U.S. patent number 8,735,414 [Application Number 13/259,717] was granted by the patent office on 2014-05-27 for indole derivatives and methods for antiviral treatment.
This patent grant is currently assigned to PTC Therapeutics, Inc.. The grantee listed for this patent is Guangming Chen, Song Xiao Huang, Ramesh Kakarla, Gary Mitchell Karp, William Joseph Lennox, Chunshi Li, Ronggang Liu, Yalei Liu, Malcolm MacCoss, Christie Morrill, F. George Njoroge, Amin Nomeir, Steven D. Paget, Hongyu Ren, Sean W Smith, James Takasugi, Anthony A. Turpoff, Nanjing Zhang, Xiaoyan Zhang, Jin Zhu. Invention is credited to Guangming Chen, Song Xiao Huang, Ramesh Kakarla, Gary Mitchell Karp, William Joseph Lennox, Chunshi Li, Ronggang Liu, Yalei Liu, Malcolm MacCoss, Christie Morrill, F. George Njoroge, Amin Nomeir, Steven D. Paget, Hongyu Ren, Sean W Smith, James Takasugi, Anthony A. Turpoff, Nanjing Zhang, Xiaoyan Zhang, Jin Zhu.
United States Patent |
8,735,414 |
MacCoss , et al. |
May 27, 2014 |
Indole derivatives and methods for antiviral treatment
Abstract
The present invention is directed to compounds and forms and
pharmaceutical compositions thereof useful for treating a viral
infection, or for affecting viral activity by modulating viral
replication.
Inventors: |
MacCoss; Malcolm (Seakbrook
Island, SC), Njoroge; F. George (Warren, NJ), Nomeir;
Amin (Milford, NJ), Chen; Guangming (Bridgewater,
NJ), Huang; Song Xiao (New Providence, NJ), Kakarla;
Ramesh (South Glastonbury, CT), Karp; Gary Mitchell
(Princeton Junction, NJ), Lennox; William Joseph
(Bedminster, NJ), Li; Chunshi (East Brunswick, NJ), Liu;
Ronggang (Berwyn, PA), Liu; Yalei (Hillsborough, NJ),
Morrill; Christie (Green Brook, NJ), Paget; Steven D.
(Hillsborough, NJ), Smith; Sean W (New Brunswick, NJ),
Takasugi; James (Lawrenceville, NJ), Turpoff; Anthony A.
(Hillsborough, NJ), Ren; Hongyu (Dayton, NJ), Zhang;
Nanjing (Princeton, NJ), Zhang; Xiaoyan (Belle Mead,
NJ), Zhu; Jin (Raritan, NJ) |
Applicant: |
Name |
City |
State |
Country |
Type |
MacCoss; Malcolm
Njoroge; F. George
Nomeir; Amin
Chen; Guangming
Huang; Song Xiao
Kakarla; Ramesh
Karp; Gary Mitchell
Lennox; William Joseph
Li; Chunshi
Liu; Ronggang
Liu; Yalei
Morrill; Christie
Paget; Steven D.
Smith; Sean W
Takasugi; James
Turpoff; Anthony A.
Ren; Hongyu
Zhang; Nanjing
Zhang; Xiaoyan
Zhu; Jin |
Seakbrook Island
Warren
Milford
Bridgewater
New Providence
South Glastonbury
Princeton Junction
Bedminster
East Brunswick
Berwyn
Hillsborough
Green Brook
Hillsborough
New Brunswick
Lawrenceville
Hillsborough
Dayton
Princeton
Belle Mead
Raritan |
SC
NJ
NJ
NJ
NJ
CT
NJ
NJ
NJ
PA
NJ
NJ
NJ
NJ
NJ
NJ
NJ
NJ
NJ
NJ |
US
US
US
US
US
US
US
US
US
US
US
US
US
US
US
US
US
US
US
US |
|
|
Assignee: |
PTC Therapeutics, Inc. (South
Plainfield, NJ)
|
Family
ID: |
42257856 |
Appl.
No.: |
13/259,717 |
Filed: |
April 5, 2010 |
PCT
Filed: |
April 05, 2010 |
PCT No.: |
PCT/US2010/029923 |
371(c)(1),(2),(4) Date: |
March 28, 2012 |
PCT
Pub. No.: |
WO2010/117932 |
PCT
Pub. Date: |
October 14, 2010 |
Prior Publication Data
|
|
|
|
Document
Identifier |
Publication Date |
|
US 20120184574 A1 |
Jul 19, 2012 |
|
Related U.S. Patent Documents
|
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
|
61166893 |
Apr 6, 2009 |
|
|
|
|
Current U.S.
Class: |
514/275; 548/518;
544/331; 546/256 |
Current CPC
Class: |
C07D
405/14 (20130101); A61P 31/22 (20180101); C07D
409/14 (20130101); A61P 29/00 (20180101); A61P
31/12 (20180101); A61P 1/16 (20180101); C07D
401/14 (20130101); A61P 31/16 (20180101); C07D
401/04 (20130101); C07D 417/14 (20130101); C07D
403/04 (20130101); A61P 31/18 (20180101); C07D
413/14 (20130101); A61P 31/14 (20180101); A61P
31/20 (20180101) |
Current International
Class: |
A61K
31/506 (20060101); C07D 401/02 (20060101); C07D
405/02 (20060101); C07D 209/04 (20060101) |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
|
|
|
|
|
|
|
1162196 |
|
Dec 2001 |
|
EP |
|
2004065367 |
|
Aug 2004 |
|
WO |
|
2006019831 |
|
Feb 2006 |
|
WO |
|
WO 2006/019831 |
|
Feb 2006 |
|
WO |
|
WO 2008137816 |
|
Nov 2008 |
|
WO |
|
2009156462 |
|
Dec 2009 |
|
WO |
|
Other References
Johnson et al. (Heterocycles, vol. 24, No. B, 1986, 2127-2131).
cited by examiner .
Morissette et al., Advanced Drug Delivery Reviews 2004, 56,
275-300. cited by examiner .
Hamdi et al., Solvates of indomethacin. Journal of Thermal Analysis
and Calorimetry 2004, 76, 985-1001. cited by examiner .
Tan et al, Nature Review Drug Discovery, 2002, 1, 867-881. cited by
examiner .
Schafer et al. Drug Discovery Today 2008, 13 (21/22), 913-916.
cited by examiner .
International Search Report for PCT/US2010/029923, mailed Aug. 26,
2010. cited by applicant .
Written Opinion for PCT/US2010/029923, mailed Aug. 26, 2010. cited
by applicant.
|
Primary Examiner: Fetterolf; Brandon
Assistant Examiner: Muresan; Ana Z
Attorney, Agent or Firm: Hoffmann & Baron, LLP
Parent Case Text
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is the National Stage of International Application
No. PCT/US2010/029923, filed Apr. 5, 2010 which claims benefit to
provisional U.S. Ser. No. 61/166,893, filed Apr. 6, 2009, herein
incorporated by reference.
This application is related to U.S. patent application Ser. No.
13/259,386, entitled "HCV Inhibitor and Therapeutic Agent
Combinations."
Claims
What is claimed is:
1. A compound of Formula (I): ##STR00289## or a free acid, free
base, salt, isotopologue, racemate, enantiomer, diastereomer, or
stereoisomer form thereof, wherein X is hydrogen, halogen, cyano,
nitro, carboxyl, C.sub.1-8alkyl-carbonyl, C.sub.1-8alkoxy-carbonyl,
formyl, amino, C.sub.1-8alkyl-amino, amino-carbonyl,
C.sub.1-8alkyl-amino-carbonyl or C.sub.1-8alkyl-sulfonyl; Ar is
pyridinyl, pyrimidinyl or pyridazinyl; Z is C.sub.1-8alkyl,
C.sub.2-8alkenyl-C.sub.1-8alkyl, C.sub.2-8alkynyl-C.sub.1-8alkyl,
halo-C.sub.1-8alkyl, C.sub.1-8alkoxy-C.sub.1-8alkyl,
C.sub.1-8alkoxy-carbonyl, carboxyl, C.sub.3-14cycloalkyl,
C.sub.3-14cycloalkenyl, C.sub.3-14cycloalkyl-C.sub.1-8alkyl, aryl,
aryl-C.sub.1-8alkyl, heteroaryl, heteroaryl-C.sub.1-8alkyl,
heterocyclyl or heterocyclyl-C.sub.1-8alkyl, wherein each instance
of aryl and heteroaryl is optionally substituted with one, two,
three or four substituents each selected from hydroxy, cyano,
nitro, halogen, C.sub.1-8alkyl, C.sub.2-8alkenyl, C.sub.2-8alkynyl,
hydroxy-C.sub.1-8alkyl, halo-C.sub.1-8alkyl, C.sub.1-8alkoxy,
halo-C.sub.1-8alkoxy, amino, C.sub.1-8alkyl-amino,
C.sub.1-8alkoxy-C.sub.1-8alkyl, C.sub.1-8alkylthio,
C.sub.1-8alkyl-carbonyl, C.sub.1-8alkoxy-carbonyl,
C.sub.1-8alkyl-carbonyloxy or amino-sulfonyl; R.sub.1 is
--SO.sub.2--N(R.sub.5)--R.sub.6; R.sub.2 is one, two, three or four
substituents each selected from hydrogen, halogen, hydroxy, cyano,
nitro, C.sub.1-8alkyl, hydroxy-C.sub.1-8alkyl, halo-C.sub.1-8alkyl,
C.sub.2-8alkenyl, halo-C.sub.2-8alkenyl, C.sub.1-8alkoxy,
halo-C.sub.1-8alkoxy, C.sub.1-8alkoxy-C.sub.1-8alkyl,
C.sub.1-8alkyl-carbonyl, C.sub.1-8alkoxy-carbonyl,
C.sub.1-8alkyl-carbonyloxy,
C.sub.1-8alkyl-carbonyloxy-C.sub.1-8alkyl,
C.sub.1-8alkyl-carbonyloxy-C.sub.1-8alkoxy, amino,
C.sub.1-8alkyl-amino, amino-C.sub.1-8alkyl,
C.sub.1-8alkyl-amino-C.sub.1-8alkyl, amino-C.sub.1-8alkoxy,
C.sub.1-8alkyl-amino-C.sub.1-8alkoxy,
C.sub.1-8alkoxy-C.sub.1-8alkyl-amino-C.sub.1-8alkoxy,
amino-C.sub.1-8alkyl-amino-C.sub.1-8alkoxy,
C.sub.1-8alkyl-amino-C.sub.1-8alkyl-amino-C.sub.1-8alkoxy,
C.sub.1-8alkoxy-carbonyl-amino, carboxyl-amino, amino-carbonyl,
amino-carbonyl-amino, C.sub.1-8alkyl-amino-carbonyl-amino,
C.sub.1-8alkylthio, C.sub.1-8alkyl-sulfinyl,
C.sub.1-8alkyl-sulfonyl, C.sub.1-8alkyl-sulfonyl-amino,
C.sub.3-14cycloalkyl, C.sub.3-14cycloalkyl-C.sub.1-8alkyl,
C.sub.3-14cycloalkyl-C.sub.1-8alkoxy, C.sub.3-14cycloalkyloxy,
aryl, aryl-C.sub.1-8alkyl, aryl-C.sub.1-8alkoxy, aryloxy,
aryl-carbonyl-amino, heteroaryl, heteroaryl-C.sub.1-8alkyl,
heteroaryl-C.sub.1-8alkoxy, heteroaryloxy, heterocyclyl,
heterocyclyl-C.sub.1-8alkyl, heterocyclyl-C.sub.1-8alkoxy,
heterocyclyloxy or heterocyclyl-carbonyloxy, wherein each instance
of aryl, heteroaryl and heterocyclyl is optionally substituted with
one, two, three or four substituents each selected from halogen,
cyano, C.sub.1-8alkyl, C.sub.1-8alkoxy,
C.sub.1-8alkoxy-C.sub.1-8alkyl, amino, C.sub.1-8alkyl-amino,
amino-C.sub.1-8alkyl or C.sub.1-8alkyl-amino-C.sub.1-8alkyl;
R.sub.5 is hydrogen; R.sub.6 is hydrogen, C.sub.1-8alkyl,
hydroxy-C.sub.1-8alkyl, halo-C.sub.1-8alkyl, cyano-C.sub.1-8alkyl,
C.sub.1-8alkoxy-C.sub.1-8alkyl, amino-C.sub.1-8alkyl,
C.sub.1-8alkyl-amino-C.sub.1-8alkyl, C.sub.1-8alkyl-carbonyl,
C.sub.1-8alkoxy-carbonyl, C.sub.3-14cycloalkyl,
C.sub.3-14cycloalkyl-C.sub.1-8alkyl, aryl, aryl-C.sub.1-8alkyl,
heteroaryl, heteroaryl-C.sub.1-8alkyl, heterocyclyl or
heterocyclyl-C.sub.1-8alkyl, wherein each instance of aryl,
heteroaryl, heterocyclyl and C.sub.3-14cycloalkyl is optionally
substituted with one or two substituents each selected from
halogen, C.sub.1-8alkyl, halo-C.sub.1-8alkyl, C.sub.1-8alkoxy,
halo-C.sub.1-8alkoxy, amino or C.sub.1-8alkyl-amino.
2. The compound of claim 1, wherein X is selected from hydrogen,
cyano, carboxyl, amino-carbonyl or C.sub.1-8alkyl-amino-carbonyl; Z
is C.sub.1-8alkyl, C.sub.3-14cycloalkyl, C.sub.3-14cycloalkenyl,
C.sub.3-14cycloalkyl-C.sub.1-8alkyl, aryl, aryl-C.sub.1-8alkyl,
heteroaryl, heteroaryl-C.sub.1-8alkyl, heterocyclyl or
heterocyclyl-C.sub.1-8alkyl, wherein each instance of aryl and
heteroaryl is optionally substituted with a substituent selected
from cyano, halogen, C.sub.1-8alkyl, C.sub.1-8alkoxy, amino or
C.sub.1-8alkyl-amino; R.sub.2 is one, two or three substituents
each selected from hydrogen, halogen, hydroxy, cyano,
C.sub.1-8alkyl, hydroxy-C.sub.1-8alkyl, halo-C.sub.1-8alkyl,
halo-C.sub.2-8alkenyl, C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy,
C.sub.1-8alkyl-carbonyl, C.sub.1-8alkoxy-carbonyl,
C.sub.1-8alkyl-carbonyloxy, amino, C.sub.1-8alkyl-amino,
amino-C.sub.1-8alkyl, C.sub.1-8alkyl-amino-C.sub.1-8alkyl,
C.sub.1-8alkylthio, C.sub.1-8alkyl-sulfinyl,
C.sub.1-8alkyl-sulfonyl, C.sub.3-14cycloalkyl,
C.sub.3-14cycloalkyl-C.sub.1-8alkyl,
C.sub.3-14cycloalkyl-C.sub.1-8alkoxy, C.sub.3-14cycloalkyloxy,
heteroaryl, heteroaryl-C.sub.1-8alkyl, heteroaryl-C.sub.1-8alkoxy,
heteroaryloxy, heterocyclyl, heterocyclyl-C.sub.1-8alkyl,
heterocyclyl-C.sub.1-8alkoxy or heterocyclyloxy, wherein
heteroaryloxy is optionally substituted with a cyano substituent;
R.sub.6 is hydrogen, C.sub.1-8alkyl, hydroxy-C.sub.1-8alkyl,
halo-C.sub.1-8alkyl, cyano-C.sub.1-8alkyl, C.sub.3-14cycloalkyl or
C.sub.3-14cycloalkyl-C.sub.1-8alkyl, wherein each instance of
C.sub.3-14cycloalkyl is optionally substituted with one or two
substituents each selected from halogen, C.sub.1-8alkyl or
halo-C.sub.1-8alkyl.
3. The compound of claim 1, wherein X is cyano; Z is
C.sub.1-8alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,
cyclohexenyl, cyclopropyl-methyl, phenyl, thiazolyl, pyridinyl,
pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl or tetrahydrofuran,
wherein phenyl is optionally substituted with a substituent
selected from cyano, halogen, C.sub.1-8alkyl or C.sub.1-8alkoxy;
R.sub.2 is one, two or three substituents each selected from
hydrogen, halogen, hydroxy, cyano, C.sub.1-8alkyl,
halo-C.sub.1-8alkyl, halo-C.sub.2-8alkenyl, C.sub.1-8alkoxy,
halo-C.sub.1-8alkoxy, C.sub.1-8alkylthio, C.sub.1-8alkykl-sulfinyl,
C.sub.1-8alkyl-sulfonyl, cyclopropyl, cyclobutyl, cyclobutoxy,
pyridinyloxy, pyrimidinyloxy, pyrazinyloxy or morpholinyl, wherein
pyridinyl and pyrazinyl are each optionally substituted with a
cyano substituent; R.sub.6 is hydrogen, C.sub.1-8alkyl,
hydroxy-C.sub.1-8alkyl, halo-C.sub.1-8alkyl, cyano-C.sub.1-8alkyl,
cyclopropyl, cyclobutyl or 1-cyclopropyl-ethyl, wherein each
instance of cyclopropyl and cyclobutyl is optionally substituted
with one or two substituents each selected from halogen,
C.sub.1-8alkyl or halo-C.sub.1-8alkyl.
4. The compound of claim 1, wherein the isotopologue is
deuterium.
5. The compound of claim 4, wherein R.sub.2 is C.sub.1-8alkyl
wherein from 1 to 3 hydrogen atoms are optionally replaced with
deuterium; R.sub.6 is C.sub.1-8alkyl wherein from 1 to 3 hydrogen
atoms are optionally replaced with deuterium or halo-C.sub.1-8alkyl
wherein from 1 to 3 hydrogen atoms are optionally replaced with
deuterium.
6. A compound of Formula (Ia): ##STR00290## or a free acid, free
base, salt, isotopologue, racemate, enantiomer, diastereomer, or
stereoisomer form thereof, wherein X is hydrogen, halogen, cyano,
nitro, carboxyl, C.sub.1-8alkyl-carbonyl, C.sub.1-8alkoxy-carbonyl,
formyl, amino, C.sub.1-8alkyl-amino, amino-carbonyl,
C.sub.1-8alkyl-amino-carbonyl or C.sub.1-8alkyl-sulfonyl; Ar is
pyridinyl, pyrimidinyl or pyridazinyl; Z is C.sub.1-8alkyl,
C.sub.2-8alkenyl-C.sub.1-8alkyl, C.sub.2-8alkynyl-C.sub.1-8alkyl,
halo-C.sub.1-8alkyl, C.sub.1-8alkoxy-C.sub.1-8alkyl,
C.sub.1-8alkoxy-carbonyl, carboxyl, C.sub.3-14cycloalkyl,
C.sub.3-14cycloalkenyl, C.sub.3-14cycloalkyl-C.sub.1-8alkyl, aryl,
aryl-C.sub.1-8alkyl, heteroaryl, heteroaryl-C.sub.1-8alkyl,
heterocyclyl or heterocyclyl-C.sub.1-8alkyl, wherein each instance
of aryl and heteroaryl is optionally substituted with one, two,
three or four substituents each selected from hydroxy, cyano,
nitro, halogen, C.sub.1-8alkyl, C.sub.2-8alkenyl, C.sub.2-8alkynyl,
hydroxy-C.sub.1-8alkyl, halo-C.sub.1-8alkyl, C.sub.1-8alkoxy,
halo-C.sub.1-8alkoxy, amino, C.sub.1-8alkyl-amino,
C.sub.1-8alkoxy-C.sub.1-8alkyl, C.sub.1-8alkylthio,
C.sub.1-8alkyl-carbonyl, C.sub.1-8alkoxy-carbonyl,
C.sub.1-8alkyl-carbonyloxy or amino-sulfonyl; R.sub.1 is
--SO.sub.2--N(R.sub.5)--R.sub.6; R.sub.5 is hydrogen; R.sub.6 is
hydrogen, C.sub.1-8alkyl, hydroxy-C.sub.1-8alkyl,
halo-C.sub.1-8alkyl, cyano-C.sub.1-8alkyl,
C.sub.1-8alkoxy-C.sub.1-8alkyl, amino-C.sub.1-8alkyl,
C.sub.1-8alkyl-amino-C.sub.1-8alkyl, C.sub.1-8alkyl-carbonyl,
C.sub.1-8alkoxy-carbonyl, C.sub.3-14cycloalkyl,
C.sub.3-14cycloalkyl-C.sub.1-8alkyl, aryl, aryl-C.sub.1-8alkyl,
heteroaryl, heteroaryl-C.sub.1-8alkyl, heterocyclyl or
heterocyclyl-C.sub.1-8alkyl, wherein each instance of aryl,
heteroaryl, heterocyclyl and C.sub.3-14cycloalkyl is optionally
substituted with one or two substituents each selected from
halogen, C.sub.1-8alkyl, halo-C.sub.1-8alkyl, C.sub.1-8alkoxy,
halo-C.sub.1-8alkoxy, amino or C.sub.1-8alkyl-amino; R.sub.8 is
hydrogen, halogen or C.sub.1-8alkoxy; R.sub.9 is hydrogen, halogen,
hydroxy, cyano, nitro, C.sub.1-8alkyl, halo-C.sub.1-8alkyl,
C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy, C.sub.1-8alkyl-carbonyl,
C.sub.1-8alkoxy-carbonyl, amino, C.sub.1-8alkyl-amino,
amino-C.sub.1-8alkyl, C.sub.1-8alkyl-amino-C.sub.1-8alkyl,
C.sub.1-8alkylthio, C.sub.3-14cycloalkyl,
C.sub.3-14cycloalkyl-C.sub.1-8alkoxy, aryl, aryl-C.sub.1-8alkoxy,
heteroaryl, heteroaryl-C.sub.1-8alkoxy, heterocyclyl or
heterocyclyl-C.sub.1-8alkoxy, wherein each instance of
C.sub.3-14cycloalkyl, aryl, heteroaryl and heterocyclyl is
optionally substituted with one, two, three or four substituents
each selected from halogen, cyano, C.sub.1-8alkyl, C.sub.1-8alkoxy,
C.sub.1-8alkoxy-C.sub.1-8alkyl, amino, C.sub.1-8alkyl-amino,
amino-C.sub.1-8alkyl or C.sub.1-8alkyl-amino-C.sub.1-8alkyl;
R.sub.10 is hydrogen, halogen, hydroxy, cyano, nitro,
C.sub.1-8alkyl, halo-C.sub.1-8alkyl, C.sub.2-8alkenyl,
halo-C.sub.2-8alkenyl, hydroxy-C.sub.1-8alkyl, C.sub.1-8alkoxy,
halo-C.sub.1-8alkoxy, C.sub.1-8alkoxy-C.sub.1-8alkyl,
C.sub.1-8alkyl-carbonyl, C.sub.1-8alkoxy-carbonyl,
C.sub.1-8alkyl-carbonyloxy,
C.sub.1-8alkyl-carbonyloxy-C.sub.1-8alkoxy, amino,
C.sub.1-8alkyl-amino, amino-C.sub.1-8alkyl,
C.sub.1-8alkyl-amino-C.sub.1-8alkyl, amino-C.sub.1-8alkoxy,
C.sub.1-8alkyl-amino-C.sub.1-8alkoxy,
C.sub.1-8alkoxy-C.sub.1-8alkyl-amino-C.sub.1-8alkoxy,
amino-C.sub.1-8alkyl-amino-C.sub.1-8alkoxy,
C.sub.1-8alkyl-amino-C.sub.1-8alkyl-amino-C.sub.1-8alkoxy,
C.sub.1-8alkoxy-carbonyl-amino, carboxyl-amino, amino-carbonyl,
amino-carbonyl-amino, C.sub.1-8alkyl-amino-carbonyl-amino,
C.sub.1-8alkylthio, C.sub.1-8alkyl-sulfinyl,
C.sub.l-8alkyl-sulfonyl, C.sub.1-8alkyl-sulfonyl-amino,
C.sub.3-14cycloalkyl, C.sub.3-14cycloalkyl-C.sub.1-8alkyl,
C.sub.3-14cycloalkyl-C.sub.1-8alkoxy, C.sub.3-14cycloalkyloxy,
aryl, aryl-C.sub.1-8alkyl, aryl-C.sub.1-8alkoxy, aryloxy,
aryl-carbonyl-amino, heteroaryl, heteroaryl-C.sub.1-8alkyl,
heteroaryl-C.sub.1-8alkoxy, heteroaryloxy, heterocyclyl,
heterocyclyl-C.sub.1-8alkyl, heterocyclyl-C.sub.1-8alkoxy,
heterocyclyloxy or heterocyclyl-carbonyloxy, wherein each instance
of C.sub.3-14cycloalkyl, aryl, heteroaryl and heterocyclyl is
optionally substituted with one, two, three or four substituents
each selected from halogen, cyano, C.sub.1-8alkyl, C.sub.1-8alkoxy,
C.sub.1-8alkoxy-C.sub.1-8alkyl, amino, C.sub.1-8alkyl-amino,
amino-C.sub.1-8alkyl or C.sub.1-8alkyl-amino-C.sub.1-8alkyl; and
R.sub.11 is hydrogen, halogen, hydroxy, cyano, nitro,
C.sub.1-8alkyl, halo-C.sub.1-8alkyl, C.sub.1-8alkoxy,
halo-C.sub.1-8alkoxy, C.sub.1-8alkyl-carbonyl,
C.sub.1-8alkoxy-carbonyl, C.sub.1-8alkyl-carbonyloxy or
C.sub.1-8alkyl-carbonyloxy-C.sub.1-8alkyl.
7. The compound of claim 6, wherein R.sub.8 is hydrogen or halogen;
R.sub.9 is hydrogen, halogen, hydroxy, cyano, C.sub.1-8alkyl,
halo-C.sub.1-8alkyl, C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy,
C.sub.1-8alkylthio or C.sub.3-14cycloalkyl; R.sub.10 is hydrogen,
halogen, hydroxy, cyano, C.sub.1-8alkyl, halo-C.sub.1-8alkyl,
halo-C.sub.2-8alkenyl, C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy,
C.sub.1-8alkylthio, C.sub.3-14cycloalkyl, C.sub.3-14cycloalkyloxy,
heteroaryloxy or heterocyclyl, wherein heteroaryloxy is optionally
substituted with a cyano substituent; and R.sub.11 is hydrogen or
halogen.
8. The compound of claim 6, wherein R.sub.9 is hydrogen, halogen,
hydroxy, cyano, C.sub.1-8alkyl, halo-C.sub.1-8alkyl,
C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy, C.sub.1-8alkylthio or
cyclopropyl; and R.sub.10 is hydrogen, halogen, hydroxy, cyano,
C.sub.1-8alkyl, halo-C.sub.1-8alkyl, halo-C.sub.2-8alkenyl,
C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy, C.sub.1-8alkylthio,
cyclopropyl, cyclobutyl, cyclobutoxy, pyridinyloxy, pyrimidinyloxy,
pyrazinyloxy or morpholinyl, wherein pyridinyl and pyrazinyl are
optionally substituted with a cyano substituent.
9. The compound of claim 1, wherein the compound or a free acid,
free base, salt, isotopologue, racemate, enantiomer, diastereomer,
or stereoisomer form thereof is selected from:
6-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-yl]-N-(propan-2-
-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-yl]-N-cyclobuty-
lpyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-propyl-1H-indol-2-yl]-N-(propan-2-yl)pyr-
idine-3-sulfonamide,
5-[3-cyano-1-cyclobutyl-6-(cyclobutyloxy)-1H-indol-2-yl]-N-(propan-2-yl)p-
yridine-2-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-(propan-2-yl)pyridine-3-
-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]-N-(propan-2-yl)p-
yridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-(propan-2-yl)pyrid-
ine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-cyclopropyl-1H-indol-2-yl)-N-(propan-2-yl)pyrid-
ine-3-sulfonamide,
N-tert-butyl-6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)pyridine-3-su-
lfonamide,
6-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(-
propan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(p-
ropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-(propan-2-yl)-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(propan--
2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-1H-indol-2-yl]-N-(pr-
opan-2-yl)pyridine-3-sulfonamide,
6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(propan-2-yl)pyridine-3-
-sulfonamide,
N-tert-butyl-6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)pyridine-3-su-
lfonamide,
6-[3-cyano-1-cyclobutyl-6-(propan-2-ylsulfanyl)-1H-indol-2-yl]--
N-(propan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(propan-2--
yl)pyridine-3-sulfonamide,
N-tert-butyl-6-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol-2-yl]-
pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-5-(difluoromethoxy)-1H-indol-2-yl]-N-(propan-2-yl-
)pyridine-3-sulfonamide,
N-tert-butyl-6-[3-cyano-1-cyclobutyl-5-(difluoromethoxy)-1H-indol-2-yl]py-
ridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-5-(difluoromethoxy)-1H-indol-2-yl]-N-(propan-2-y-
l)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-5-(trifluoromethoxy)-1H-indol-2-yl]-N-(propan-2-y-
l)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(1,3-difluo-
ropropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-5-(trifluoromethoxy)-1H-indol-2-yl]-N-(1,3-difluo-
ropropan-2-yl)pyridine-3-sulfonamide,
5-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(propan-2-y-
l)pyridine-2-sulfonamide,
5-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-(propan-2-yl)pyrid-
ine-2-sulfonamide,
5-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(propan-2-yl)pyridine-2-
-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyridine-3-sulfonamide,
6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-difluor-
opropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-5-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-difluor-
opropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-5-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-difluo-
ropropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-5-(trifluoromethoxy)-1H-indol-2-yl]-N-(1,3-diflu-
oropropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-(1,3-difluoropropa-
n-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difl-
uoropropan-2-yl)pyridine-3-sulfonamide,
6-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyridine-3-sulfonamide,
5-[3-cyano-1-cyclopropyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(propan-2-y-
l)pyridine-2-sulfonamide,
5-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-1H-indol-2-yl]-N-(pr-
opan-2-yl)pyridine-2-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,-
3-difluoropropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopropyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-difluo-
ropropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropro-
pan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-propyl-1H-indol-2-yl]-N-(1,3-difluoropro-
pan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(tetrahydrofuran-3-yl)-1H-indol-2-yl]-N-(1,3-difluo-
ropropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(tetrahydrofuran-3-yl)-1H-indol-2-yl]-N-(propan-2-y-
l)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-ethyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-yl-
)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-difluo-
ropropan-2-yl)pyridine-3-sulfonamide,
6-(6-chloro-3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-(1,3-difluorop-
ropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(propan-2-yl-
)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(propan-2-y-
l)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,1,1-trif-
luoropropan-2-yl)pyridine-3-sulfonamide,
6-{3-cyano-6-methyl-1-[(3R)-tetrahydrofuran-3-yl]-1H-indol-2-yl}-N-(1,3-d-
ifluoropropan-2-yl)pyridine-3-sulfonamide,
6-{3-cyano-6-methyl-1-[(3R)-tetrahydrofuran-3-yl]-1H-indol-2-yl}-N-(propa-
n-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-fluoro-1H-indol-2-yl]-N-(1,3-difluorop-
ropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]-N-(1,3-difluorop-
ropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethoxy)-1H-indol-2-yl]-N-(propan-2-
-yl)pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan--
2-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan--
2-yl)pyridine-3-sulfonamide,
6-[6-chloro-3-cyano-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-(1,3-difluorop-
ropan-2-yl)pyridine-3-sulfonamide,
6-[6-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan--
2-yl)pyridine-3-sulfonamide,
6-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyridine-3-sulfonamide,
6-[5-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan--
2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-7-fluoro-1H-indol-2-yl)-N-(propan-2-yl)pyridine--
3-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1-fluoro-2-
-methylpropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(1-
,3-difluoropropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-(propan-2-yl)-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(1,3-dif-
luoropropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(1,3-diflu-
oropropan-2-yl)pyridine-3-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-(propan-2-yl)pyrim-
idine-5-sulfonamide,
6-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyridine-3-sulfonamide,
6-[5-chloro-3-cyano-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-(1,3-difluorop-
ropan-2-yl)pyridine-3-sulfonamide,
2-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-(propan-2-yl)pyrimidin-
e-5-sulfonamide,
6-[3-cyano-6-ethyl-1-(propan-2-yl)-1H-indol-2-yl]-N-(propan-2-yl)pyridine-
-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1-fluoro-2--
methylpropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,1,1-trifl-
uoropropan-2-yl)pyridine-3-sulfonamide,
6-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyridine-3-sulfonamide,
6-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan--
2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl]-N-(1,3-difluorop-
ropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyridine-3-sulfonamide,
6-[3-cyano-6-cyclopropyl-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropr-
opan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-cyclopropyl-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-(1,3-difl-
uoropropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-(1,3-difluoroprop-
an-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-(1,1,1-trifluorop-
ropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-7-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyridine-3-sulfonamide,
6-(7-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyridine-3-sulfonamide,
6-(6-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)pyridine-3-sulfonamid-
e,
6-(3-cyano-1-cyclohexyl-6-cyclopropyl-1H-indol-2-yl)-N-(1,3-difluoropro-
pan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[1-(trifluor-
omethyl)cyclopropyl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[1-(trifluo-
romethyl)cyclopropyl]pyridine-3-sulfonamide,
6-(3-cyano-6-cyclopropyl-1-phenyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan-
-2-yl)pyridine-3-sulfonamide,
2-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-(propan-2-yl)pyrimidine-
-5-sulfonamide,
2-(3-cyano-1-cyclohexyl-6-methyl-1H-indol-2-yl)-N-(propan-2-yl)pyrimidine-
-5-sulfonamide,
6-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(propan-2-yl-
)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-difluor-
opropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methoxy-1H-indol-2-yl)-N-(propan-2-yl)-
pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methoxy-1H-indol-2-yl)-N-(1,3-difluoro-
propan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethenyl)-1H-indol-2-yl]-N-(1,3-dif-
luoropropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclohexyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(1,3-difluo-
ropropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[1-(trifluor-
omethyl)cyclobutyl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-5-fluoro-1H-indol-2-yl)-N-(1,3-difl-
uoropropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-difluorop-
ropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1,6-dicyclopropyl-1H-indol-2-yl)-N-(propan-2-yl)pyridine-3-sul-
fonamide,
6-[6-chloro-3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl-
]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-6-methyl-1-phenyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-yl)py-
ridine-3-sulfonamide,
6-(5-chloro-3-cyano-1-phenyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-yl)py-
ridine-3-sulfonamide,
6-(3-cyano-5-fluoro-1-phenyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-yl)py-
ridine-3-sulfonamide,
2-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(propan-2-yl)pyrimidine-
-5-sulfonamide,
2-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(propan-2-yl)pyrimidine-
-5-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(propan-2-y-
l)pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(propan-2--
yl)pyrimidine-5-sulfonamide,
6-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(1S)-1-cyclopropyleth-
yl]pyridine-3-sulfonamide,
6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(1S)-1-cyclopropylethy-
l]pyridine-3-sulfonamide,
2-[5-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N-(propan-2-yl)pyrimid-
ine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-(propan-2-yl)pyrimidine-
-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyrimidine-5-sulfonamide,
2-[3-cyano-5-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-(propan-2-yl)pyrimid-
ine-5-sulfonamide,
2-[3-cyano-6-cyclopropyl-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-(propan-2-
-yl)pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-(propan-2-yl)pyri-
midine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-(1,3-difluoropropa-
n-2-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(propan-2-yl-
)pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,1,1-trifl-
uoropropan-2-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-difluor-
opropan-2-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(1S)-1-cycl-
opropylethyl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-[(1S)-1-cyclopropy-
lethyl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyrimidine-5-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl]-N-(1,3-difluorop-
ropan-2-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan--
2-yl)pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyrimidine-5-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,-
3-difluoropropan-2-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difl-
uoropropan-2-yl)pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-(propan-2-yl)pyrimidine-
-5-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-6-fluoro-1H-indol-2-yl]-N-(propan-2-yl)p-
yrimidine-5-sulfonamide,
2-[3-cyano-6-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-(propan-2-yl)pyrimid-
ine-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-(propan-2-yl)pyrimidin-
e-5-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[(1S)-1-cyclopropylethy-
l]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-[(1S)-1-cyclopropyleth-
yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-[(1S)-1-cyclopropylethy-
l]pyridine-3-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-cyclopropyl-5-fluoro-1H-indol-2-yl)-N-(1,3-difl-
uoropropan-2-yl)pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-difluorop-
ropan-2-yl)pyrimidine-5-sulfonamide,
6-(3-cyano-1,6-dicyclopropyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-yl)py-
ridine-3-sulfonamide,
2-(3-cyano-1,6-dicyclopropyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-yl)py-
rimidine-5-sulfonamide,
2-(6-chloro-3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-(1,3-difluorop-
ropan-2-yl)pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-5-fluoro-6-methoxy-1H-indol-2-yl)-N-(1,3-difluoro-
propan-2-yl)pyrimidine-5-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(1S)-1-cycl-
opropylethyl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(1S)-1-cyc-
lopropylethyl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-[1-(trifluoromethy-
l)cyclopropyl]pyridine-3-sulfonamide,
6-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(1S)-1-cyclopropylethy-
l]pyridine-3-sulfonamide,
6-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(1S)-1-cyclopropyleth-
yl]pyridine-3-sulfonamide,
2-[6-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N-(propan-2-yl)pyrimid-
ine-5-sulfonamide,
2-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyridine-3-sulfonamide,
2-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-(propan-2-yl)pyrimidin-
e-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyrimidine-5-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(methylsulfanyl)-1H-indol-2-yl]-N-(1,3-difluoro-
propan-2-yl)pyridine-3-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(methylsulfanyl)-1H-indol-2-yl]-N-(1,3-difluoro-
propan-2-yl)pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyrimidine-5-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-6-fluoro-1H-indol-2-yl]-N-(1,3-difluorop-
ropan-2-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-6-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan--
2-yl)pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyrimidine-5-sulfonamide,
2-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-(propan-2-yl)pyrimid-
ine-5-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl]-N-(propan-2-yl)p-
yrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(propan-2-yl)pyrimidine-
-5-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-1H-indol-2-yl]-N-(pr-
opan-2-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-yl]-N-(propan-2-
-yl)pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N-(propan-2-yl)pyrimidin-
e-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-(1,3-difluoroprop-
an-2-yl)pyrimidine-5-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(1S)-1-cyc-
lopropylethyl]pyridine-3-sulfonamide,
2-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyrimidine-5-sulfonamide,
2-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(1,3-difluo-
ropropan-2-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(1,3-diflu-
oropropan-2-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-difluor-
opropan-2-yl)pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-[(2R)-1,1,1-triflu-
oropropan-2-yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluoropr-
opan-2-yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluorop-
ropan-2-yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluorop-
ropan-2-yl]pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2R)-1,1,1--
trifluoropropan-2-yl]pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(propan-2-yl)-1H-indol-2-yl]-N-(propan-2-yl)pyr-
imidine-5-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropro-
pan-2-yl)pyrimidine-5-sulfonamide,
2-[5-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan--
2-yl)pyrimidine-5-sulfonamide,
2-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyrimidine-5-sulfonamide,
2-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(propan-2-yl)pyrimidin-
e-5-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[1-(trifluoromethyl)cy-
clopropyl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(2R)-1,1,1-
-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
2-(3-cyano-1-cyclohexyl-6-cyclopropyl-1H-indol-2-yl)-N-(1,3-difluoropropa-
n-2-yl)pyrimidine-5-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2R)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2R)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2R)-1,1,1-trifluor-
opropan-2yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl]-N-[(2R)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
2-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyridine-3-sulfonamide,
2-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-(propan-2-yl)pyrimidine-
-5-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[(1S)-1-cyclopropylethy-
l]pyridine-3-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(1S)-1-cyclopropylethy-
l]pyrimidine-5-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl]-N-[(1S)-1-cyclop-
ropylethyl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[(1S)-1-cyclopropyleth-
yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N-[(1S)-1-cyclopropyleth-
yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N-[(1S)-1-cyclopropylet-
hyl]pyrimidine-5-sulfonamide,
2-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-yl]-N-[(1S)-1-c-
yclopropylethyl]pyrimidine-5-sulfonamide,
2-[3-cyano-6-(difluoromethoxy)-1-propyl-1H-indol-2-yl]-N-[(1S)-1-cyclopro-
pylethyl]pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(1S)-1-cyc-
lopropylethyl]pyrimidine-5-sulfonamide,
6-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2R)-1,1,1-trifluor-
opropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-[(2R)-1,1,1-trifl-
uoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-[(2R)-1,1,1-triflu-
oropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclohexyl-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluorop-
ropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-fluoro-1H-indol-2-yl]-N-[(2R)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-6-fluoro-1-propyl-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluoropropan-
-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluorop-
ropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluorop-
ropan-2-yl]pyridine-3-sulfonamide,
2-[5-chloro-3-cyano-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-(1,3-difluorop-
ropan-2-yl)pyrimidine-5-sulfonamide,
6-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluorop-
ropan-2-yl]pyridine-3-sulfonamide,
6-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluorop-
ropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-6-methoxy-1H-indol-2-yl]-N-(1,3-
-difluoropropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]-N-(1,3-difluoropro-
pan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(2-fluorophenyl)-1H-indol-2-yl]-N-(1,3-d-
ifluoropropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(4-fluorophenyl)-1H-indol-2-yl]-N-(1,3-d-
ifluoropropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyridine-3-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N-(1,3-difluoropropan-2-
-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-6-(difluoromethoxy)-1-propyl-1H-indol-2-yl]-N-(1,3-difluoropro-
pan-2-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-difluo-
ropropan-2-yl)pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyridine-3-sulfonamide,
2-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-[(1S)-1-cyclopropy-
lethyl]pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl]-N-[(1S)-1-cyclop-
ropylethyl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(1S)-1-cyclopropylethy-
l]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-dihydro-
xypropan-2-yl)pyridine-3-sulfonamide,
2-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclohexyl-6-methyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyrimidine-5-sulfonamide,
2-[3-cyano-5-(difluoromethoxy)-1-ethyl-1H-indol-2-yl]-N-(propan-2-yl)pyri-
midine-5-sulfonamide,
6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(3,3-difluorocyclobutyl-
)pyridine-3-sulfonamide,
6-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(3,3-difluorocyclobutyl-
)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(3,3-difluorocyclobutyl-
)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N-(3,3-difluorocyclobut-
yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-(3,3-difluorocyclo-
butyl)pyridine-3-sulfonamide,
6-[3-cyano-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan-
-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-dif-
luoropropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-[(1S)-1-cyclopropylethy-
l]pyridine-3-sulfonamide,
2-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-(propan-2-yl)pyrimidine-
-5-sulfonamide,
6-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[1-(trifluoromethyl)cy-
clobutyl]pyridine-3-sulfonamide,
2-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-[(1S)-1-cycloprop-
ylethyl]pyrimidine-5-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl]-N-[1-(trifluorom-
ethyl)cyclopropyl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[1-(trifluoromethyl)cyc-
lopropyl]pyridine-3-sulfonamide,
2-[6-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan--
2-yl)pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-ethyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-yl-
)pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(pyridin-4-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan-
-2-yl)pyridine-3-sulfonamide,
2-(3-cyano-6-methyl-1-phenyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-yl)py-
rimidine-5-sulfonamide,
6-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-[(1S)-1-cyclopropylethy-
l]pyridine-3-sulfonamide,
6-(3-cyano-1,6-dicyclobutyl-1H-indol-2-yl)-N-[(1S)-1-cyclopropylethyl]pyr-
idine-3-sulfonamide,
2-(3-cyano-1,6-dicyclobutyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-yl)pyr-
imidine-5-sulfonamide,
2-(3-cyano-1,6-dicyclobutyl-1H-indol-2-yl)-N-(propan-2-yl)pyrimidine-5-su-
lfonamide,
6-(3-cyano-1,6-dicyclobutyl-1H-indol-2-yl)-N-(propan-2-yl)pyrid-
ine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-(1,3-diflu-
oropropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2S)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1-cyanoethy-
l)pyridine-3-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]-N-(1,3-difluorop-
ropan-2-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]-N-(propan-2-yl)p-
yrimidine-5-sulfonamide,
6-[3-cyano-1-cyclohexyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(2R)-1,1,1-
-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclohexyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(1S)-1-cyc-
lopropylethyl]pyridine-3-sulfonamide,
2-[3-cyano-1-cyclohexyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(1,3-difluo-
ropropan-2-yl)pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyridine-3-sulfonamide,
6-[3-cyano-1-(propan-2-yl)-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(1S)-1--
cyclopropylethyl]pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(-
1S)-1-cyclopropylethyl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-ethyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-ethyl-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-ethyl-1H-indol-2-yl)-N-[(1S)-1-cyclopropylethy-
l]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-[1-(trifluoromethyl)cy-
clopropyl]pyridine-3-sulfonamide,
2-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(propan-2-yl)pyrimidin-
e-5-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(fluoromethyl)-1H-indol-2-yl]-N-(propan-2-yl)py-
rimidine-5-sulfonamide,
6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(fluoromethyl)-1H-indol-2-yl]-N-[(1S)-1-cyclopr-
opylethyl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(fluoromethyl)-1H-indol-2-yl]-N-(1,3-difluoropr-
opan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(fluoromethyl)-1H-indol-2-yl]-N-[(2R)-1,1,1-tri-
fluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(1S)-1-cy-
clopropylethyl]pyridine-3-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(morpholin-4-yl)-1H-indol-2-yl]-N-(1,3-difluoro-
propan-2-yl)pyrimidine-5-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(morpholin-4-yl)-1H-indol-2-yl]-N-(1,3-difluoro-
propan-2-yl)pyridine-3-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2S)-1,1,1--
trifluoropropan-2-yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-[(2S)-1,1,1-triflu-
oropropan-2-yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2S)-1,1,1-
-trifluoropropan-2-yl]pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-[1-(trifluoromethyl)cy-
clopropyl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[1-(trifluoromethyl)cyc-
lopropyl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[1-(trifluoromethyl)cyc-
lopropyl]pyridine-3-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]-N-(1,3-difluoro-
propan-2-yl)pyrimidine-5-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]-N-(1,3-difluoro-
propan-2-yl)pyridine-3-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]-N-(propan-2-yl)-
pyrimidine-5-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]-N-(propan-2-yl)-
pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]-N-[(2R)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]-N-[(1S)-1-cyclo-
propylethyl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(4-methoxyphenyl)-1H-indol-2-yl]-N-(1,3-difluoropro-
pan-2-yl)pyridine-3-sulfonamide,
2-[3-cyano-5-fluoro-1-(4-methoxyphenyl)-1H-indol-2-yl]-N-(1,3-difluoropro-
pan-2-yl)pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-ethyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropro-
pan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-ethyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropro-
pan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2S)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1,6-dicyclobutyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-yl)pyr-
idine-3-sulfonamide,
6-(3-cyano-6-cyclobutyl-1-cyclopentyl-1H-indol-2-yl)-N-[(2R)-1,1,1-triflu-
oropropan-2-yl]pyridine-3-sulfonamide,
2-[3-cyano-6-cyclopropyl-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-(1,3-difl-
uoropropan-2-yl)pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluorop-
ropan-2-yl]pyridine-3-sulfonamide,
6-(3,5-dicyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropropan-
-2-yl]pyridine-3-sulfonamide,
6-[3,6-dicyano-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-(1,3-difluoropropan-
-2-yl)pyridine-3-sulfonamide,
6-[3,6-dicyano-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-(propan-2-yl)pyridi-
ne-3-sulfonamide,
6-[3,6-dicyano-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluo-
ropropan-2-yl]pyridine-3-sulfonamide,
N-[(1S)-1-cyclopropylethyl]-6-[3,6-dicyano-1-(cyclopropylmethyl)-1H-indol-
-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluorop-
ropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl]-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclohexyl-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluor-
opropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(4-methylphenyl)-1H-indol-2-yl]-N-(1,3-difluoroprop-
an-2-yl)pyridine-3-sulfonamide,
2-[3-cyano-5-fluoro-1-(4-methylphenyl)-1H-indol-2-yl]-N-(propan-2-yl)pyri-
midine-5-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(6-chloro-3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(fluoromethyl)-1H-indol-2-yl]-N-(1,3-difluoropr-
opan-2-yl)pyrimidine-5-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(fluoromethyl)-1H-indol-2-yl]-N-[(2S)-1,1,1-tri-
fluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]-N-[(2S)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluorop-
ropan-2-yl]pyridine-3-sulfonamide,
6-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluorop-
ropan-2-yl]pyridine-3-sulfonamide,
N-[(1S)-1-cyclopropylethyl]-2-(3,5-dicyano-1-cyclopentyl-1H-indol-2-yl)py-
rimidine-5-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(4-fluorophenyl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-[(2S)-1,1,1-triflu-
oropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(2S)-1,1,1-
-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-(1,1,1-trifluoro-2-met-
hylpropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2-yl]-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2-yl]-N-(1,3-difluorop-
ropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-ethyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
2-[3-cyano-1-cyclobutyl-5-(fluoromethyl)-1H-indol-2-yl]-N-(1,3-difluoropr-
opan-2-yl)pyrimidine-5-sulfonamide,
6-[3-cyano-1-cyclobutyl-5-(difluoromethyl)-1H-indol-2-yl]-N-(1,3-difluoro-
propan-2-yl)pyridine-3-sulfonamide,
2-[3-cyano-1-cyclobutyl-5-(difluoromethyl)-1H-indol-2-yl]-N-(1,3-difluoro-
propan-2-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclobutyl-5-(difluoromethyl)-1H-indol-2-yl]-N-[(2S)-1,1,1-t-
rifluoropropan-2-yl]pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-ethyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,1,1-trif-
luoro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifl-
uoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide,
6-[3-cyano-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluo-
ropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2-yl]-N-(propan-2-yl)p-
yrimidine-5-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2-yl]-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluorop-
ropan-2-yl]pyrimidine-5-sulfonamide,
2-(3,5-dicyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropropan-
-2-yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluorop-
ropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-fluoro-1H-indol-2-yl]-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide,
2-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide,
2-[3-cyano-6-(difluoromethoxy)-1-propyl-1H-indol-2-yl]-N-[(2S)-1,1,1-trif-
luoropropan-2-yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifl-
uoropropan-2-yl]pyrimidine-5-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl]-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyrimidine-5-sulfonamide,
2-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluor-
opropan-2-yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluorop-
ropan-2-yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluorop-
ropan-2-yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoro-
propan-2-yl]pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-difluoro-
propan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
2-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyrimidine-5-sulfonamide,
6-[3-cyano-1-(cyclohex-2-en-1-yl)-5-fluoro-1H-indol-2-yl]-N-[(2R)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclohex-2-en-1-yl)-5-fluoro-1H-indol-2-yl]-N-[(2S)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
2-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyrimidine-5-sulfonamide,
2-[6-chloro-3-cyano-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-(propan-2-yl)pyrimidine-
-5-sulfonamide,
2-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluorop-
ropan-2-yl]pyrimidine-5-sulfonamide,
2-[6-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluor-
opropan-2-yl]pyrimidine-5-sulfonamide,
2-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluorop-
ropan-2-yl]pyrimidine-5-sulfonamide,
2-[5-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluor-
opropan-2-yl]pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclobutyl-7-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-7-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-difluorop-
ropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-7-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-difluoro-
propan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-7-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-[(1S)-1-cyclopropyle-
thyl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[(1S)-1-cyclopropyleth-
yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluorop-
ropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluorop-
ropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N-[(1S)-1-cyclopropyleth-
yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoro-
propan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluoro-
propan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N-[(1S)-1-cyclopropylet-
hyl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-[(1S)-1-cycloprop-
ylethyl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluorop-
ropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[6-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluo-
ropropan-2-yl]pyridine-3-sulfonamide,
6-[6-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan-
-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(propan-2-yl)pyridi-
ne-3-sulfonamide,
6-(3-cyano-6-methyl-1-phenyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropropan-
-2-yl]pyridine-3-sulfonamide,
6-(5-chloro-3-cyano-1-phenyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropropan-
-2-yl]pyridine-3-sulfonamide,
6-[5-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluo-
ropropan-2-yl]pyridine-3-sulfonamide,
6-[5-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan-
-2-yl)pyridine-3-sulfonamide,
6-(5-chloro-3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(1,3-difluorop-
ropan-2-yl)pyridine-3-sulfonamide,
6-(5-chloro-3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(5-chloro-3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
2-(5-chloro-3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(1,3-difluorop-
ropan-2-yl)pyrimidine-5-sulfonamide,
2-(5-chloro-3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyrimidine-5-sulfonamide,
2-[6-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluo-
ropropan-2-yl]pyrimidine-5-sulfonamide,
2-[6-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan-
-2-yl)pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-methoxy-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluorop-
ropan-2-yl]pyridine-3-sulfonamide,
2-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(propan-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trif-
luoropropan-2-yl]pyrimidine-5-sulfonamide,
6-[3-cyano-1,6-di(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan-2-yl)-
pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropr-
opan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2-yl]-N-[(2R)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclohexyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(2S)-1,1,1-
-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-di-
fluoropropan-2-yl)pyridine-3-sulfonamide,
6-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
2-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyrimidine-5-sulfonamide,
2-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyrimidine-5-sulfonamide,
6-(3,6-dicyano-1-cyclobutyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-yl)pyr-
idine-3-sulfonamide,
2-(3,6-dicyano-1-cyclobutyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-yl)pyr-
imidine-5-sulfonamide,
6-(3,6-dicyano-1-cyclobutyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropropan--
2-yl]pyridine-3-sulfonamide,
6-(3,6-dicyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-yl)py-
ridine-3-sulfonamide,
2-(3,6-dicyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-yl)py-
rimidine-5-sulfonamide,
6-(3,6-dicyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropropan-
-2-yl]pyridine-3-sulfonamide,
2-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(1S)-1-cycl-
opropylethyl]pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2S)-1,1,1--
trifluoropropan-2-yl]pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(propan-2-yl-
)pyrimidine-5-sulfonamide,
2-[3-cyano-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluo-
ropropan-2-yl]pyrimidine-5-sulfonamide,
2-[3-cyano-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluo-
ropropan-2-yl]pyrimidine-5-sulfonamide,
6-[3-cyano-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluo-
ropropan-2-yl]pyridine-3-sulfonamide,
2-[3-cyano-6-(difluoromethoxy)-1-(4-fluorophenyl)-1H-indol-2-yl]-N-(1,3-d-
ifluoropropan-2-yl)pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(1,1,1-trifluoro-2-meth-
ylpropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,1,1-trifl-
uoro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-(1,1,1-trifluoro-2-meth-
ylpropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-ethyl-1H-indol-2-yl)-N-(1,1,1-trifluoro-2-methy-
lpropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-fluoro-5-methyl-1H-indol-2-yl)-N-(1,3-difluoro-
propan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-fluoro-5-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2R)-1,1,1-trifluor-
opropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluorop-
ropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-[6-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(1S)-1-cyclopropyl-
ethyl]pyridine-3-sulfonamide,
6-[6-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2R)-1,1,1-trifluo-
ropropan-2-yl]pyridine-3-sulfonamide,
6-[5-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(1S)-1-cyclopropyl-
ethyl]pyridine-3-sulfonamide,
6-[5-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2R)-1,1,1-trifluo-
ropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-fluoro-5-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-fluoro-5-methyl-1H-indol-2-yl)-N-(1,3-difluorop-
ropan-2-yl)pyridine-3-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluorop-
ropan-2-yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-[(1S)-1-cyclopropylethy-
l]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-[(1S)-1-cyclopropyleth-
yl]pyrimidine-5-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-6-fluoro-1H-indol-2-yl]-N-[(1S)-1-cyclop-
ropylethyl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-[(1S)-1-cyclopropylethy-
l]pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-methoxy-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluorop-
ropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-cyclopropyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-difluorop-
ropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-cyclopropyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluo-
ropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan-
-2-yl)pyridine-3-sulfonamide,
6-(6-chloro-3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-(1,3-difluorop-
ropan-2-yl)pyridine-3-sulfonamide,
6-(6-chloro-3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
2-(6-chloro-3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-(propan-2-yl)p-
yrimidine-5-sulfonamide,
6-(3-cyano-1-cyclopentyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-(1,3-difl-
uoropropan-2-yl)pyridine-3-sulfonamide,
6-(6-chloro-3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-yl)pyridi-
ne-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclohexyl-6-methyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyridine-3-sulfonamide,
6-(6-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
6-(6-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
2-(6-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyrimidine-5-sulfonamide,
2-(6-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclohexyl-6-methoxy-1H-indol-2-yl)-N-[(2R)-1,1,1-trifluorop-
ropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclohexyl-6-methoxy-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluorop-
ropan-2-yl]pyridine-3-sulfonamide,
2-(3-cyano-1-cyclohexyl-6-methoxy-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyrimidine-5-sulfonamide,
6-(6-chloro-3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-(1,3-difluoro-
propan-2-yl)pyridine-3-sulfonamide,
6-(6-chloro-3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
2-(6-chloro-3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-(propan-2-yl)-
pyrimidine-5-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2-yl]-N-(1,3-difluorop-
ropan-2-yl)pyrimidine-5-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2-yl]-N-[(1S)-1-cyclop-
ropylethyl]pyridine-3-sulfonamide,
2-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-(propan-2-yl)pyrimidine-
-5-sulfonamide,
2-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan-2-y-
l)pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-[(1S)-1-cyclopropylethy-
l]pyrimidine-5-sulfonamide,
2-[3-cyano-5-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-[(1S)-1-cyclopropyle-
thyl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-[(1S)-1-cyclopropyleth-
yl]pyrimidine-5-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]-N-[(1S)-1-cyclop-
ropylethyl]pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-(1,3-diflu-
oropropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2R)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-5-(difluoromethyl)-1H-indol-2-yl]-N-(1,3-difluor-
opropan-2-yl)pyridine-3-sulfonamide,
2-[3-cyano-1-cyclopentyl-5-(difluoromethyl)-1H-indol-2-yl]-N-(1,3-difluor-
opropan-2-yl)pyrimidine-5-sulfonamide,
6-[3-cyano-1-cyclopentyl-5-(difluoromethyl)-1H-indol-2-yl]-N-[(2S)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-5-(difluoromethyl)-1H-indol-2-yl]-N-[(2R)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,1,1-trifluo-
ro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-diflu-
oropropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N-(1,-
3-difluoropropan-2-yl)pyridine-3-sulfonamide,
N-tert-butyl-6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]py-
ridine-3-sulfonamide,
2-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[(1S)-1-cyclopropylethy-
l]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[(1S)-1-cyclopropylethy-
l]pyrimidine-5-sulfonamide,
2-[3-cyano-5-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluor-
opropan-2-yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluorop-
ropan-2-yl]pyrimidine-5-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyrimidine-5-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-methoxy-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyridine-3-sulfonamide,
2-(3-cyano-1-cyclobutyl-5-methoxy-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyrimidine-5-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]pyridine-3-sulf-
onamide,
6-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]-N-[(2R)-1,1,1-trif-
luoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-4,6-difluoro-5-methyl-1H-indol-2-yl)-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-4,6-difluoro-5-methyl-1H-indol-2-yl)-N-(1,3-diflu-
oropropan-2-yl)pyridine-3-sulfonamide,
2-(3-cyano-1-cyclobutyl-7-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-difluorop-
ropan-2-yl)pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclopentyl-4,6-difluoro-5-methyl-1H-indol-2-yl)-N-(1,3-difl-
uoropropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-4,6-difluoro-5-methyl-1H-indol-2-yl)-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyridine-3-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2-yl]-N-[(1S)-1-cyclop-
ropylethyl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-[(1S)-1-cyclopropyleth-
yl]pyrimidine-5-sulfonamide,
2-[3-cyano-5-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-[(1S)-1-cyclopropyle-
thyl]pyrimidine-5-sulfonamide,
6-[3-cyano-5-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-[(1S)-1-cyclopropyle-
thyl]pyridine-3-sulfonamide,
2-[3-cyano-5-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-(propan-2-yl)pyrimid-
ine-5-sulfonamide,
2-[3-cyano-5-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluor-
opropan-2-yl]pyrimidine-5-sulfonamide,
2-[3-cyano-5-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan--
2-yl)pyrimidine-5-sulfonamide,
1-cyclobutyl-6-(difluoromethoxy)-2-(5-sulfamoylpyridin-2-yl)-1H-indole-3--
carboxamide,
2-(3-cyano-1-cyclobutyl-5-methoxy-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluorop-
ropan-2-yl]pyrimidine-5-sulfonamide,
2-(3-cyano-1-cyclobutyl-5-methoxy-1H-indol-2-yl)-N-[(1S)-1-cyclopropyleth-
yl]pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-methoxy-1H-indol-2-yl)-N-(1,3-difluoropropan-2-
-yl)pyridine-3-sulfonamide,
2-(3-cyano-1-cyclopentyl-5-methoxy-1H-indol-2-yl)-N-(1,3-difluoropropan-2-
-yl)pyrimidine-5-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N-(1-
,3-difluoropropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-6-hydroxy-1H-indol-2-yl)-N-(1,3-difluor-
opropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-6-hydroxy-1H-indol-2-yl)-N-[(2S)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-(1,1,1-tri-
fluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-7-fluoro-6-methyl-1H-indol-2-yl)-N-(1,1,1-trifluo-
ro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-7-fluoro-6-methyl-1H-indol-2-yl)-N-(1,1,1-triflu-
oro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-(1,1,1-tr-
ifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
1-cyclobutyl-6-(difluoromethoxy)-2-{5-[(1,3-difluoropropan-2-yl)sulfamoyl-
]pyridin-2-yl}-1H-indole-3-carboxamide,
1-cyclobutyl-6-cyclopropyl-2-{5-[(1,3-difluoropropan-2-yl)sulfamoyl]pyrid-
in-2-yl}-1H-indole-3-carboxamide,
6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,1,1-t-
rifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-cyclopropyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,1,1-trifluo-
ro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-6-methyl-1-phenyl-1H-indol-2-yl)-N-(1,1,1-trifluoro-2-methylpr-
opan-2-yl)pyridine-3-sulfonamide,
2-(3-cyano-1-cyclopentyl-7-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-difluoro-
propan-2-yl)pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[1-(trifluoromethyl)cyc-
lobutyl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[1-(trifluo-
romethyl)cyclobutyl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2S)-1,1,1-
-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[(1S)-1-cy-
clopropylethyl]pyridine-3-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-(1,3-diflu-
oropropan-2-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[(1S)-1-cy-
clopropylethyl]pyrimidine-5-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-(1,3-difl-
uoropropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[(1S)-1-c-
yclopropylethyl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-(1,1,1-tr-
ifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
2-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[(1S)-1-c-
yclopropylethyl]pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-(propan-2-
-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-(1,3-difl-
uoropropan-2-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide,
6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifl-
uoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-(1,1,1-trifluoro--
2-methylpropan-2-yl)pyridine-3-sulfonamide,
2-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-(propan-2-yl)pyrimidin-
e-5-sulfonamide,
6-[3-cyano-5-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-[(1S)-1-cyclopropyle-
thyl]pyridine-3-sulfonamide,
2-(3-cyano-1-cyclohexyl-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropr-
opan-2-yl]pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-[(1S)-1-cyclopropylethy-
l]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-(1,1,1-trifluoro-2-met-
hylpropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-(1,3-difluoroprop-
an-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
2-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]-N-(1,3-difluoropro-
pan-2-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]-N-[(2S)-1,1,1-trif-
luoropropan-2-yl]pyrimidine-5-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]-N-(1,1,1-trifluoro-
-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[1-(trifluorom-
ethyl)cyclopropyl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-4-fluoro-5-methyl-1H-indol-2-yl)-N-(1,1,1-triflu-
oro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-4-fluoro-5-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-(-
1,3-difluoropropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[-
(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[-
(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-(-
propan-2-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-(-
1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide,
2-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[1-(trif-
luoromethyl)cyclopropyl]pyridine-3-sulfonamide,
N-tert-butyl-6-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]pyridi-
ne-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-4-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-4-fluoro-6-methyl-1H-indol-2-yl)-N-(1,1,1-triflu-
oro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-4-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-4-fluoro-6-methyl-1H-indol-2-yl)-N-[1-(trifluoro-
methyl)cyclopropyl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-4-fluoro-6-methyl-1H-indol-2-yl)-N-[1-(trifluorom-
ethyl)cyclopropyl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-5-fluoro-1H-indol-2-yl)-N-[(2R)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-[(2R)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-(1,3-d-
ifluoropropan-2-yl)pyridine-3-sulfonamide,
6-[5-chloro-3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-[1-(trifluorom-
ethyl)cyclopropyl]pyridine-3-sulfonamide,
2-(3-cyano-1-cyclopentyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-(1,3-difluorop-
ropan-2-yl)pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-(1,3-difluorop-
ropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-tri-
fluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-[(2R)-1,1,1-tri-
fluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-[1-(trifluorome-
thyl)cyclopropyl]pyridine-3-sulfonamide,
N-tert-butyl-6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)pyr-
idine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[1-(trifluoro-
methyl)cyclopropyl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1-methylcycl-
opropyl)pyridine-3-sulfonamide,
6-[1-cyclobutyl-6-(difluoromethoxy)-5-methyl-1H-indol-2-yl]-N-[(2S)-1,1,1-
-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-ethyl-1H-indol-2-yl]-N-[(2S-
)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N-[(2-
R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(4-fluorophenyl)-1H-indol-2-yl]-N-[(2R)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-cyclopropyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide,
N-tert-butyl-6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)pyri-
dine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-cyclopropylpyr-
idine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-[1-(trifl-
uoromethyl)cyclopropyl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(propan-2-yl)p-
yridine-3-sulfonamide,
2-(3-cyano-1-cyclopentyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-(1,3-difl-
uoropropan-2-yl)pyrimidine-5-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(pyridine-2-yl)-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[5-chloro-3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1--
methylcyclopropyl)pyridine-3-sulfonamide,
2-[5-chloro-3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,-
3-difluoropropan-2-yl)pyrimidine-5-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-methyl-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-5-fluoro-1H-indol-2-yl)-N-[(2R)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-(1,1,1-
-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(4-fluorophenyl)-1H-indol-2-yl]-N-[1-(tr-
ifluoromethyl)cyclopropyl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-methyl-1H-indol-2-yl]-N-[(2-
R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-[1-(triflu-
oromethyl)cyclopropyl]pyridine-3-sulfonamide,
2-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-(1,3-diflu-
oropropan-2-yl)pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-methoxy-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N-
-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2R)-1,1,1-trifluo-
ropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluo-
ro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2R)-1,1,1-trifl-
uoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-hydroxy-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(5-bromo-3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N-(1,-
1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifl-
uoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclohexyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
2-(3-cyano-1-cyclohexyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyrimidine-5-sulfonamide,
6-(3-cyano-1-cyclohexyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,1,1-triflu-
oro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-
-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclopentyl-5-fluoro-6-methyl-1-
H-indole-3-carboxamide,
6-(5-bromo-3-cyano-1-cyclobutyl-6-hydroxy-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-(methylsulfanyl)-1H-indol-2-
-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,1,1-trifluoro-2--
methylpropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(4-fluorophenyl)-1H-indol-2-yl]-N-(1,1,1-
-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2R)-1,1,1-trifl-
uoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-(1,1,1-trifluoro--
2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[1-(tr-
ifluoromethyl)cyclopropyl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-hydroxy-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(5-bromo-3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-hydroxy-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-methoxy-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2R)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-5-(2,2-difluoroethyl)-1H-indol-2-yl]-N-(1-methylc-
yclopropyl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-5-fluoro-1H-indol-2-yl]-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2R)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
1-cyclopentyl-5-fluoro-6-methyl-2-(5-{[(2R)-1,1,1-trifluoropropan-2-yl]su-
lfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-cyclopentyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]su-
lfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-cyclopentyl-5-fluoro-6-methyl-2-{5-[(1,1,1-trifluoro-2-methylpropan-2-y-
l)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide,
6-[3-cyano-1-cyclobutyl-5-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoroprop-
an-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclohexyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,1,1-trifluo-
ro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
1-cyclohexyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]sul-
famoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-cyclohexyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]sul-
famoyl}pyrimidin-2-yl)-1H-indole-3-carboxamide,
6-[5-chloro-3-cyano-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifl-
uoropropan-2-yl]pyridine-3-sulfonamide,
N-tert-butyl-6-(3-cyano-1-cyclohexyl-5-fluoro-6-methyl-1H-indol-2-yl)pyri-
dine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-6-hydroxy-1H-indol-2-yl)-N-[(2S)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N-(di-
fluoromethyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N-[(-
2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
1-cyclohexyl-5-fluoro-6-methyl-2-{5-[(1,1,1-trifluoro-2-methylpropan-2-yl-
)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide,
1-cyclohexyl-5-fluoro-6-methyl-2-(5-sulfamoylpyridin-2-yl)-1H-indole-3-ca-
rboxamide,
1-cyclohexyl-5-fluoro-6-methyl-2-(5-{[(2R)-1,1,1-trifluoropropa-
n-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide methyl
1-cyclohexyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl}py-
ridin-2-yl)-1H-indole-3-carboxylate
1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-2-(5-{[(2R)-1,1,1-trifluoropro-
pan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide
N-tert-butyl-6-(3-cyano-1-cyclobutyl-5-fluoro-6-hydroxy-1H-indol-2-yl)pyr-
idine-3-sulfonamide
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]pyridi-
ne-3-sulfonamide
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclobutyl-6-(difluoromethoxy)--
5-fluoro-1H-indole-3-carboxamide
6-{3-cyano-5-fluoro-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-indol-2-yl}-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methoxy-1H-indol-2-yl)-N-[(2S)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide
6-(3-cyano-1-cyclobutyl-6-ethoxy-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide
6-[1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N-[(2S)-1,1,1-
-trifluoropropan-2-yl]pyridine-3-sulfonamide
6-(1-cyclobutyl-5-fluoro-6-hydroxy-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoro-
propan-2-yl]pyridine-3-sulfonamide,
1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-2-{5-[(1,1,1-trifluoro-2-methyl-
propan-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide,
1-cyclopentyl-5-fluoro-6-methyl-2-(5-{[1-(trifluoromethyl)cyclopropyl]sul-
famoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-cyclobutyl-6-cyclopropyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan-2-y-
l]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-cyclobutyl-5-fluoro-6-methyl-2-(5-{[(2R)-1,1,1-trifluoropropan-2-yl]sul-
famoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
5-chloro-1-cyclobutyl-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]sul-
famoyl}pyrimidin-2-yl)-1H-indole-3-carboxamide,
5-chloro-1-cyclobutyl-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]sul-
famoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
5-chloro-1-cyclobutyl-6-methyl-2-(5-{[(2R)-1,1,1-trifluoropropan-2-yl]sul-
famoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-chloro-1-cyclobutyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]sul-
famoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-cyclobutyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]sul-
famoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluorobutan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(3-methylpyridin-2-yl)-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-{3-cyano-5-fluoro-6-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-indol-
-2-yl}-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
1-cyclohexyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl}py-
ridin-2-yl)-1H-indole-3-carboxylic acid,
6-[3-cyano-5-fluoro-1-(5-fluoropyridin-2-yl)-6-methyl-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(5-cyanopyridin-2-yl)-5-fluoro-6-methyl-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(5-nitropyridin-2-yl)-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
5-chloro-1-cyclobutyl-2-[5-(propan-2-ylsulfamoyl)pyrimidin-2-yl]-1H-indol-
e-3-carboxamide,
1-cyclohexyl-6-(difluoromethoxy)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]s-
ulfamoyl}pyrimidin-2-yl)-1H-indole-3-carboxamide,
1-cyclohexyl-6-(difluoromethoxy)-2-[5-(propan-2-ylsulfamoyl)pyrimidin-2-y-
l]-1H-indole-3-carboxamide,
5-fluoro-1-(pyridin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoy-
l}pyridin-2-yl)-1H-indole-3-carboxamide,
6-[3-cyano-5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indol-2-yl]--
N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indol-2-yl]--
N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
N-tert-butyl-6-[3-cyano-5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-
-indol-2-yl]pyridine-3-sulfonamide,
2-[3-cyano-5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide, methyl
1-cyclopentyl-5-fluoro-6-methyl-2-{5-[(1,1,1-trifluoro-2-methylpropan-2-y-
l)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxylate, methyl
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclopentyl-5-fluoro-6-methyl-1-
H-indole-3-carboxylate, methyl
1-cyclopentyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]su-
lfamoyl}pyridin-2-yl)-1H-indole-3-carboxylate,
6-(3-cyano-1-cyclobutyl-5-methoxy-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
1-cyclopentyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]su-
lfamoyl}pyridin-2-yl)-1H-indole-3-carboxylic acid,
6-(1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoro-
propan-2-yl]pyridine-3-sulfonamide,
1-cyclopentyl-5-fluoro-N,6-dimethyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-y-
l]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-cyclopentyl-N-ethyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-
-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-cyclopentyl-5-fluoro-6-methyl-N-(propan-2-yl)-2-(5-{[(2S)-1,1,1-trifluo-
ropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
N-tert-butyl-6-(3-cyano-1-cyclobutyl-6-ethyl-5-fluoro-1H-indol-2-yl)pyrid-
ine-3-sulfonamide,
1-cyclopentyl-5-fluoro-6-methyl-2-{5-[(1,1,1-trifluoro-2-methylpropan-2-y-
l)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxylic acid,
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclopentyl-5-fluoro-6-methyl-1-
H-indole-3-carboxylic acid
5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-2-(5-{[(2R)-1,1,1-trifluor-
opropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-2-{5-[(1,1,1-trifluoro-2-m-
ethylpropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide,
5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-2-(5-{[(2S)-1,1,1-trifluor-
opropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
methyl
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclobutyl-5-fluoro-6-methyl-1H-
-indole-3-carboxylate, methyl
1-cyclobutyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]sul-
famoyl}pyridin-2-yl)-1H-indole-3-carboxylate,
6-[3-cyano-1-cyclobutyl-5-fluoro-6-(methylsulfanyl)-1H-indol-2-yl]-N-[(2S-
)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-4-fluoro-1H-indol-2--
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
methyl
1-cyclobutyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]sul-
famoyl}pyrimidin-2-yl)-1H-indole-3-carboxylate,
1-cyclobutyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]sul-
famoyl}pyrimidin-2-yl)-1H-indole-3-carboxylic acid,
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclobutyl-5-fluoro-6-methyl-1H-
-indole-3-carboxylic acid,
6-[3-cyano-6-ethyl-5-fluoro-1-(5-fluoropyridin-2-yl)-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-chloro-1-cyclobutyl-2-[5-(propan-2-ylsulfamoyl)pyrimidin-2-yl]-1H-indol-
e-3-carboxamide,
1-cyclobutyl-2-[5-(propan-2-ylsulfamoyl)pyrimidin-2-yl]-6-(trifluorometho-
xy)-1H-indole-3-carboxamide,
1-cyclopentyl-2-[5-(propan-2-ylsulfamoyl)pyrimidin-2-yl]-6-(trifluorometh-
oxy)-1H-indole-3-carboxamide,
1-cyclopentyl-5-fluoro-N,N,6-trimethyl-2-(5-{[(2S)-1,1,1-trifluoropropan--
2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-[3-cyano-6-(difluoromethoxy)-4-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[5-chloro-3-cyano-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-propyl-1H-indol-2-yl]-N-[(2S)-1-
,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-5-fluoro-1H-indol-2--
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-propyl-1H-indol-2-yl]-N-[(2R)-1-
,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-5-fluoro-1H-indol-2--
yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N-(1,-
1,1-trifluorobutan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N-phe-
nylpyridine-3-sulfonamide,
1-cyclobutyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]sul-
famoyl}pyridin-2-yl)-1H-indole-3-carboxylic acid,
2-[5-(tert-butylsulfamoyl)pyrimidin-2-yl]-1-cyclobutyl-5-fluoro-6-methyl--
1H-indole-3-carboxylic acid,
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclobutyl-5-fluoro-N,6-dimethy-
l-1H-indole-3-carboxamide,
6-(3-cyano-1-cyclobutyl-5-hydroxy-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-4-fluoro-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclopentyl-5-fluoro-N,6-dimeth-
yl-1H-indole-3-carboxamide,
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclobutyl-5-fluoro-6-methyl-1H-
-indole-3-carboxamide,
1-cyclobutyl-5-fluoro-N,6-dimethyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl-
]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
2-[5-(tert-butylsulfamoyl)pyrimidin-2-yl]-1-cyclobutyl-5-fluoro-N,6-dimet-
hyl-1H-indole-3-carboxamide,
6-[5-chloro-3-cyano-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[5-chloro-3-cyano-1-(5-fluoropyridin-2-yl)-6-methyl-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
N-tert-butyl-6-(3-cyano-1-cyclobutyl-5-hydroxy-6-methyl-1H-indol-2-yl)pyr-
idine-3-sulfonamide,
1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropro-
pan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-(3-cyano-1-cyclobutyl-5-hydroxy-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N-[1--
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide,
1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-2-(5-{[1-(trifluoromethyl)cyclo-
propyl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-4-methyl-1H-indol-2--
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-7-methyl-1H-indol-2--
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-5-fluoro-1H-indol-2--
yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-6-hydroxy-1H-indol-2-yl)-N-[1-(trifluoro-
methyl)cyclopropyl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(3-fluoropyridin-2-yl)-6-methyl-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(6-fluoropyridin-2-yl)-6-methyl-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(4-methoxypyridin-2-yl)-6-methyl-1H-indol-2-yl]-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyrazin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-cyclopropyl-5-fluoro-1-(5-fluoropyridin-2-yl)-1H-indol-2-yl]-
-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-cyclopropyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-
-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-cyclopropyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-t-
rifluorobutan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-4-met-
hyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
N-tert-butyl-6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]pyridin-
e-3-sulfonamide,
N-tert-butyl-6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-y-
l]pyridine-3-sulfonamide,
1-cyclobutyl-6-(difluoromethoxy)-4-fluoro-2-(5-{[(2S)-1,1,1-trifluoroprop-
an-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluorobutan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-5-met-
hyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclobutyl-5-hydroxy-6-methyl-1-
H-indole-3-carboxamide,
1-cyclopentyl-6-cyclopropyl-5-fluoro-2-(5-{[(2R)-1,1,1-trifluoropropan-2--
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-cyclopentyl-6-ethyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]sul-
famoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-5-fluoro-1H-indol-2-yl)-N-(1,1,1-t-
rifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
N-tert-butyl-6-(3-cyano-1-cyclopentyl-6-cyclopropyl-5-fluoro-1H-indol-2-y-
l)pyridine-3-sulfonamide,
1-cyclobutyl-5-hydroxy-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]su-
lfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-cyclopentyl-5-methoxy-6-methyl-2-(5-{[(2R)-1,1,1-trifluoropropan-2-yl]s-
ulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-cyclohexyl-5-fluoro-6-methyl-2-(5-{[1-(trifluoromethyl)cyclopropyl]sulf-
amoyl}pyridin-2-yl)-1H-indole-3-carboxylic acid,
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-5-methyl-N-[(2S-
)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
1-cyclopentyl-6-cyclopropyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan-2--
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-(difluoromethoxy)-4-fluoro-1-(propan-2-yl)-2-(5-{[(2S)-1,1,1-trifluorop-
ropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-(cyclopropylmethyl)-6-(difluoromethoxy)-4-fluoro-2-(5-{[(2S)-1,1,1-trif-
luoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-cyclopentyl-5-hydroxy-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]s-
ulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-4-methyl-N-[(2S-
)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifl-
uoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(3-fluoropyridin-2-yl)-5-methyl-1H-indol-2-yl]-N-[(2S)-1,1,1-
-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-methyl-1-(pyrazin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluo-
ropropan-2-yl]pyridine-3-sulfonamide,
5-methyl-1-(pyrimidin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]sulfam-
oyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-[3-cyano-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-4-methyl-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-4-methyl-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-y-
l]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-cyclopentyl-6-cyclopropyl-5-fluoro-2-{5-[(1,1,1-trifluoro-2-methylpropa-
n-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-4-methyl-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-4-methyl-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-4-methyl-N-
-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-4-methyl-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
N-tert-butyl-6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl-
]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclohexyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[1-(trifluorom-
ethyl)cyclopropyl]pyridine-3-sulfonamide,
1-cyclohexyl-5-fluoro-6-methyl-2-(5-{[1-(trifluoromethyl)cyclopropyl]sulf-
amoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-(3-cyano-1-cyclobutyl-6-ethyl-4-methoxy-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-(1,1,1-tr-
ifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-(1-methyl-
cyclopropyl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N-(1-
,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-2-{5-[(1,1,1-trifluoro-2-methy-
lpropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[1-(trifl-
uoromethyl)cyclopropyl]pyridine-3-sulfonamide
6-[3-cyano-5-fluoro-6-methyl-1-(5-methylpyrazin-2-yl)-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
6-[3-cyano-5-fluoro-1-(4-methoxypyrimidin-2-yl)-6-methyl-1H-indol-2-yl]-N-
-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-5-methyl-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-2-methyl-N-[(2S-
)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
N-tert-butyl-6-[6-ethyl-5-fluoro-3-(methylsulfonyl)-1-(pyrimidin-2-yl)-1H-
-indol-2-yl]pyridine-3-sulfonamide
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-5-methyl-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
1-cyclopentyl-6-ethyl-5-fluoro-2-{5-[(1,1,1-trifluoro-2-methylpropan-2-yl-
)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide,
1-cyclopentyl-6-ethyl-5-fluoro-2-(5-{[1-(trifluoromethyl)cyclopropyl]sulf-
amoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-[3-cyano-5-fluoro-6-methyl-1-(4-methylpyrimidin-2-yl)-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
5-fluoro-6-methyl-1-(pyridin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl-
]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
5-fluoro-6-methyl-1-(pyrazin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl-
]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
5-fluoro-1-(5-fluoropyridin-2-yl)-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropro-
pan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
5-fluoro-1-(6-fluoropyridin-2-yl)-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropro-
pan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2R)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2R)-1,1,1-
-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(5-fluoropyridin-2-yl)-1H-indol-2-yl]-N-[(2-
R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-2-methyl-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
N-tert-butyl-6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]p-
yridine-3-sulfonamide,
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-6-ethyl-5-fluoro-1-(pyridin-2-yl)-
-1H-indole-3-carboxamide,
N-tert-butyl-6-(3-cyano-6-ethyl-5-fluoro-1-phenyl-1H-indol-2-yl)pyridine--
3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(5-methylpyridin-2-yl)-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(4-methylpyridin-2-yl)-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-2-methyl-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-5-methyl-N-
-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-5-methyl-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-4-methyl-N--
[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-4-methyl-N-[(-
2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyridazin-3-yl)-1H-indol-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-3-yl)-1H-indol-2-yl]-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-5-yl)-1H-indol-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[6-bromo-3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-4-yl)-1H-indol-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(pyrazin-2-yl)-5-(trifluoromethyl)-1H-indol-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(pyrazin-2-yl)-5-(trifluoromethoxy)-1H-indol-2-yl]-N-[(2S)-1-
,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
N-tert-butyl-6-[3-cyano-6-ethyl-5-fluoro-1-(pyrazin-2-yl)-1H-indol-2-yl]p-
yridine-3-sulfonamide,
N-tert-butyl-6-[3-cyano-6-ethyl-5-fluoro-1-(3-fluoropyridin-2-yl)-1H-indo-
l-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-fluoro-5-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
5-fluoro-1-(3-fluoropyridin-2-yl)-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropro-
pan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-[5-fluoro-6-methyl-1-(1,3-thiazol-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
5-fluoro-6-methyl-1-(5-methylpyrazin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropro-
pan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide
5-fluoro-6-methyl-1-(4-methylpyrimidin-2-yl)-2-(5-{[(2S)-1,1,1-trifluorop-
ropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide
5-fluoro-1-(4-methoxypyrimidin-2-yl)-6-methyl-2-(5-{[(2S)-1,1,1-trifluoro-
propan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide
6-[6-acetyl-3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
6-[3-cyano-6-ethenyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1-
,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
6-ethyl-5-fluoro-1-(pyridin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]-
sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide
6-(3-cyano-1-cyclopropyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide
6-[3-cyano-5-fluoro-6-(1-hydroxyethyl)-1-(pyrimidin-2-yl)-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
5-fluoro-6-methyl-1-(pyridazin-3-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2--
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide
5-fluoro-6-methyl-1-(pyridin-3-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl-
]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide
6-[1-(5-chloropyrimidin-2-yl)-3-cyano-5-fluoro-6-methyl-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(6-methylpyrazin-2-yl)-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
5-methyl-1-(pyrazin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoy-
l}pyridin-2-yl)-1H-indole-3-carboxamide,
6-[3-cyano-6-fluoro-5-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-fluoro-5-methyl-1-(pyrimidin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2--
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-[3-cyano-6-fluoro-5-methyl-1-(pyrazin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(4-fluorophenyl)-5-methyl-1H-indol-2-yl]-N-[(2S)-1,1,1-trifl-
uoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-5-methyl-1-phenyl-1H-indol-2-yl)-N-[(2S)-1,1,1-trifluoropropan-
-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(pyrimidin-2-yl)-5-(trifluoromethyl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(6-methylpyridin-2-yl)-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(5-fluoropyrimidin-2-yl)-6-methyl-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(5-methylpyrimidin-2-yl)-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(4-fluoropyridin-2-yl)-6-methyl-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-(2-methyl-1,3-dioxolan-2-yl)-1-(pyrimidin-2-yl)-1H--
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
1-cyclohexyl-6-(difluoromethoxy)-5-fluoro-2-{5-[(1,1,1-trifluoro-2-methyl-
propan-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxylic acid,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrazin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(6-fluoropyridin-2-yl)-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(5-methylpyridin-2-yl)-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(4-methylpyridin-2-yl)-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-4-yl)-1H-indol-2-yl]-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(1,3-thiazol-2-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(1,3-thiazol-2-yl)-1H-indol-2-yl]-N-[(2S)-1-
,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(2-methylpropyl)-1H-indol-2-yl]-
-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[6-bromo-3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-tert-buty-
lpyridine-3-sulfonamide,
N-tert-butyl-6-[3,6-diacetyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]py-
ridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(2-hydroxyethyl)-1H-indol-2-yl]-
-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(1,6-dihydropyrimidin-2-yl)-6-ethyl-5-fluoro-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[1-(5-chloropyrimidin-2-yl)-3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl]-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(2-methylpyrimidin-4-yl)-1H-indol-2-yl]-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[5-fluoro-1-(2-fluoropyridin-4-yl)-6-methyl-1H-indol-2-yl]-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(5-fluoropyridin-3-yl)-6-methyl-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(5-fluoropyrimidin-2-yl)-1H-indol-2-yl]-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-chloro-6-cyclopropyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(5-fluoropyrimidin-2-yl)-5-methyl-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-fluoro-1-(5-fluoropyrimidin-2-yl)-5-methyl-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(pyrimidin-2-yl)-6-(trifluoromethyl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(pyrazin-2-yl)-6-(trifluoromethyl)-1H-indol-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(pyridin-2-yl)-6-(trifluoromethyl)-1H-indol-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-(cyclobut-
ylmethyl)pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-3-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(4-methoxypyridin-2-yl)-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoro(2-deuterium)propan-2-yl]pyridine-3-sulfonamide,
6-[5-fluoro-6-methyl-1-(1,3-thiazol-4-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[5-fluoro-6-methyl-1-(1,3,4-thiadiazol-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[5-fluoro-6-methyl-1-(1,3-thiazol-5-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(1,3-thiazol-4-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(5-fluoro-6-methylpyridin-2-yl)-6-methyl-1H-indol-2-
-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[1-(6-chloropyridin-2-yl)-3-cyano-5-fluoro-6-methyl-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-5-yl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-4-yl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[1-(3-chloropyridin-2-yl)-3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[1-(5-chloropyridin-2-yl)-3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-(prop-2-en-1-yl)-1-(pyrimidin-2-yl)-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-chloro-5-fluoro-6-(prop-2-en-1-yl)-1-(pyrimidin-2-yl)-1H-indol-2-yl]-
-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[5-fluoro-6-(prop-2-en-1-yl)-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-(2-hydroxyethyl)-1-(pyrimidin-2-yl)-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[1-(3-chloropyridin-2-yl)-3-cyano-5-fluoro-6-methyl-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-chloro-5-fluoro-6-methyl-1-(1,3,4-thiadiazol-2-yl)-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(1,3-thiazol-5-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-4-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridazin-3-yl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(5-methylpyrimidin-2-yl)-1H-indol-2-yl]-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(1,3,4-thiadiazol-2-yl)-1H-indol-2-yl]-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-2-{5-[(1,1,1-trifluoro-2-methylpropan-
-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide,
6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-2-(5-{[1-(trifluoromethyl)cyclopropyl-
]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-ethyl-5-fluoro-1-(4-methylpyridin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoroprop-
an-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-ethyl-5-fluoro-1-(5-fluoropyridin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoroprop-
an-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-ethyl-5-fluoro-1-(2-methylpyrimidin-4-yl)-2-(5-{[(2S)-1,1,1-trifluoropr-
opan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-[1-(5-chloropyridin-3-yl)-3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-{3-cyano-5-fluoro-1-[5-(hydroxymethyl)-1,3-thiazol-2-yl]-6-methyl-1H-in-
dol-2-yl}-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
methyl
2-[3-cyano-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-y-
l]sulfamoyl}pyridin-2-yl)-1H-indol-1-yl]-1,3-thiazole-5-carboxylate,
methyl
2-[3-cyano-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-y-
l]sulfamoyl}pyridin-2-yl)-1H-indol-1-yl]-1,3-thiazole-4-carboxylate,
6-[5-fluoro-6-methyl-1-(thiophen-3-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifl-
uoropropan-2-yl]pyridine-3-sulfonamide,
6-[5-fluoro-1-(furan-3-yl)-6-methyl-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluor-
opropan-2-yl]pyridine-3-sulfonamide,
6-[5-fluoro-6-methyl-1-(thiophen-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifl-
uoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(thiophen-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(furan-3-yl)-6-methyl-1H-indol-2-yl]-N-[(2S)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(thiophen-3-yl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[1-(4-chloropyridin-2-yl)-3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-ethyl-5-fluoro-1-(pyrazin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]-
sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-ethyl-5-fluoro-1-(6-fluoropyridin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoroprop-
an-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
5-chloro-1-cyclobutyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl}py-
ridin-2-yl)-1H-indole-3-carboxamide,
1-cyclobutyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl}py-
ridin-2-yl)-1H-indole-3-carboxamide,
6-[3-cyano-5-fluoro-6-methyl-1-(3-methylthiophen-2-yl)-1H-indol-2-yl]-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(4,6-difluoropyridin-2-yl)-5-fluoro-6-methyl-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(4-fluorophenyl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[1-(4-chlorophenyl)-3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(4-methylphenyl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(4-methoxyphenyl)-1H-indol-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-{3-cyano-6-ethyl-5-fluoro-1-[4-(trifluoromethyl)phenyl]-1H-indol-2-yl}--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(4-cyanophenyl)-6-ethyl-5-fluoro-1H-indol-2-yl]-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(3-fluorophenyl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(3-methylphenyl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(3-methoxyphenyl)-1H-indol-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-{3-cyano-6-ethyl-5-fluoro-1-[3-(trifluoromethyl)phenyl]-1H-indol-2-yl}--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(3-cyanophenyl)-6-ethyl-5-fluoro-1H-indol-2-yl]-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(2-fluoropyridin-4-yl)-6-methyl-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(3-fluoropyridin-4-yl)-6-methyl-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(6-fluoropyridin-3-yl)-6-methyl-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(1-methyl-1H-pyrazol-4-yl)-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(5-methyl-1,3-thiazol-2-yl)-1H-indol-2-yl]-
-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[1-(3-chlorophenyl)-3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-ethyl-5-fluoro-1-(4-fluorophenyl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-y-
l]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-(4-chlorophenyl)-6-ethyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan-2-y-
l]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-ethyl-5-fluoro-1-(4-methylphenyl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-y-
l]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-ethyl-5-fluoro-1-[4-(trifluoromethyl)phenyl]-2-(5-{[(2S)-1,1,1-trifluor-
opropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-ethyl-5-fluoro-1-(3-fluorophenyl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-y-
l]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-ethyl-5-fluoro-1-(3-methylphenyl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-y-
l]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-ethyl-5-fluoro-1-(3-methoxyphenyl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2--
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-ethyl-5-fluoro-1-[3-(trifluoromethyl)phenyl]-2-(5-{[(2S)-1,1,1-trifluor-
opropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-(3-chlorophenyl)-6-ethyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan-2-y-
l]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-[3-cyano-5-fluoro-6-methyl-1-(3-methyl-1H-pyrazol-4-yl)-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(5-methylthiophen-2-yl)-1H-indol-2-yl]-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[1-(5-chlorothiophen-2-yl)-3-cyano-5-fluoro-6-methyl-1H-indol-2-yl]-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(5-cyanothiophen-2-yl)-5-fluoro-6-methyl-1H-indol-2-yl]-N-[(-
2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(5-sulfamoylthiophen-2-yl)-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[1-(5-acetylthiophen-2-yl)-3-cyano-5-fluoro-6-methyl-1H-indol-2-yl]-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(4-methyl-1,3-thiazol-2-yl)-1H-indol-2-yl]-
-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-ethyl-5-fluoro-1-(5-methylpyridin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoroprop-
an-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-ethyl-5-fluoro-1-(pyridin-3-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]-
sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-ethyl-5-fluoro-1-(pyrimidin-4-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-y-
l]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-(3-chloropyridin-2-yl)-6-ethyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoroprop-
an-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-(5-chloropyridin-2-yl)-6-ethyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoroprop-
an-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-(5-chloropyridin-3-yl)-6-ethyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoroprop-
an-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide
6-ethyl-5-fluoro-1-(pyridin-4-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-yl]-
sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-ethyl-5-fluoro-1-(pyridazin-3-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-y-
l]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-ethyl-5-fluoro-1-(5-methylpyrimidin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropr-
opan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1-(4-chloropyridin-2-yl)-6-ethyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoroprop-
an-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-[1-(2-acetylthiophen-3-yl)-3-cyano-5-fluoro-6-methyl-1H-indol-2-yl]-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(4-methylthiophen-3-yl)-1H-indol-2-yl]-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[1-(2-chlorothiophen-3-yl)-3-cyano-5-fluoro-6-methyl-1H-indol-2-yl]-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(5-methylthiophen-3-yl)-1H-indol-2-yl]-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[5-fluoro-6-methyl-1-(1,3-oxazol-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-tri-
fluoropropan-2-yl]pyridine-3-sulfonamide,
6-[1-(5-cyanofuran-2-yl)-5-fluoro-6-methyl-1H-indol-2-yl]-N-[(2S)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(3,4-difluorophenyl)-6-ethyl-5-fluoro-1H-indol-2-yl]-N-[(2S)-
-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[1-(3-chloro-4-fluorophenyl)-3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(3-cyanofuran-2-yl)-5-fluoro-6-methyl-1H-indol-2-yl]-N-[(2S)-
-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(1,3oxazol-2-yl)-1H-indol-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-(4-cyano-1,3-oxazol-2-yl)-5fluoro-6-methyl-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(2-fluorophenyl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-{3-cyano-6-[(1,1-dideuterium)ethyl]-5-fluoro-1-(pyrimidin-2-yl)-1H-indo-
l-2-yl}-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-{3-cyano-6-[(1,1-D)ethyl]-5-fluoro-1-(pyrimidin-2-yl}-N-[(2S)-1,1,1-tri-
fluoro(2-deuterium)propan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-cyclopropyl-4-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-(1,-
1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-(1,1,1-trideuterium)methyl-1-(pyrimidin-2-yl)-1H-in-
dol-2-yl]-N-[(2S)-1,1,1-trifluoro(2-deuterium)propan-2-yl]pyridine-3-sulfo-
namide,
N-tert-butyl-6-(3-cyano-5-fluoro-6-methyl-1-phenyl-1H-indol-2-yl)p-
yridine-3-sulfonamide,
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-6-ethyl-5-fluoro-1-phenyl-1H-indo-
le-3-carboxamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2-deuterium)-
propan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluoro(2-deuterium)propan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-5-fluoro-6-(1,1,1-trideuterium)methyl-1H-indol-2--
yl]-N-[(2S)-1,1,1-trifluoro(2-deuterium)propan-2-yl]pyridine-3-sulfonamide-
,
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclohexyl-5-fluoro-6-methyl-1-
H-indole-3-carboxamide,
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-5-fluoro-6-methyl-1-phenyl-1H-ind-
ole-3-carboxamide,
N-tert-butyl-6-(3-cyano-6-cyclopropyl-5-fluoro-1-phenyl-1H-indol-2-yl)pyr-
idine-3-sulfonamide,
6-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-6-(1,1,1-trideuterium)methyl-1H-
-indol-2-yl]-N-[(2-deuterium)propan-2-yl]pyridine-3-sulfonamide.
10. The compound of claim 9, wherein the compound or a free acid,
free base, salt, isotopologue, racemate, enantiomer, diastereomer,
or stereoisomer form thereof is selected from:
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-(propan-2-yl)pyrid-
ine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-difluor-
opropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-(1,3-difluoropropa-
n-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2--
yl)pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(propan-2-yl-
)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-5-fluoro-1H-indol-2-yl)-N-(1,3-difl-
uoropropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-difluorop-
ropan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[1-(trifluoromethyl)cy-
clopropyl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2S)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-(1,1,1-trifluoro-2-met-
hylpropan-2-yl)pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-difluoro-
propan-2-yl)pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-7-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifl-
uoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclobutyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-tri-
fluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-cyclopropyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(pyridine-2-yl)-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-
-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclopentyl-5-fluoro-6-methyl-1-
H-indole-3-carboxamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
1-cyclohexyl-5-fluoro-6-methyl-2-(5-{[(2R)-1,1,1-trifluoropropan-2-yl]sul-
famoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-[3-cyano-5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indol-2-yl]--
N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-4-methyl-1H-indol-2--
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-cyclopropyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-t-
rifluorobutan-2-yl]pyridine-3-sulfonamide,
6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-y-
l]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(2-methylpropyl)-1H-indol-2-yl]-
-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(1,3-thiazol-4-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, or
6-[3-cyano-5-fluoro-6-methyl-1-(1,3,4-thiadiazol-2-yl)-1H-indol-2-yl]-N-[-
(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide.
11. The compound of claim 10, wherein the compound or free acid,
free base, salt, isotopologue, racemate, enantiomer, diastereomer,
or stereoisomer form thereof is selected from:
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indo1-2-yl]-N-[(2S)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indo1-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indo1-2-yl)-N-[(2R)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-1-(pyrimidin-2-yl)-1H-indo1-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)-1H-indo1-2-yl]-N-[(2S)-1,1,-
1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indo1-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indo1-2-yl]-N-[(2S)-1,1,1-trifl-
uoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2-yl)-1H-indo1-2-yl]-N-[(2S)-1,-
1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-cyclopropyl-1-(pyrimidin-2-yl)-1H-indo1-2-yl]-N-[(2S)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(pyrimidin-2-yl)-1H-indo1-2-yl]-
-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indo1-2-yl]-N-[(2S)-1,1-
,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-[3-cyano-6-cyclopropyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indo1-2-yl]-N-[(2-
S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-y-
l]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, or
6-[3-cyano-5-fluoro-6-methyl-1-(1
,3-thiazol-4-yl)-1H-indo1-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridi-
ne-3-sulfonamide.
12. A method for inhibiting HCV viral replication in
replicon-containing cells comprising the steps of: 1) culturing
replicon-containing cells with a compound of claim 1 for a period
of time sufficient to reduce the replicon RNA value, and 2)
comparing the replicon RNA value in replicon-containing cells
cultured with the compound of claim 1 with the replicon RNA value
in replicon-containing cells that have not been cultured with the
compound of claim 1; wherein the replicon is a hepatitis C virus
replicon.
13. A method for treating a hepatitis C viral infection in a
subject in need thereof comprising administering an effective
amount of a compound of claim 1 to the subject.
14. The method of claim 13, wherein the effective amount of a
compound of claim 1 or a form thereof is in a range of from about
0.001 mg/Kg/day to about 500 mg/Kg/day.
15. A pharmaceutical composition comprising an effective amount of
a compound of claim 1 or a form thereof in admixture with a
pharmaceutically acceptable excipient.
Description
GOVERNMENT SUPPORT
The present invention was not made with U.S. Government
support.
STATEMENT OF JOINT RESEARCH AGREEMENT
The present invention was made by or on behalf of parties to a
joint research agreement that was in effect on or before the date
the invention was made, specifically, the present invention was
made as a result of activities undertaken within the scope of the
joint research agreement to which PTC Therapeutics, Inc. and
Schering Corporation are parties.
FIELD OF THE INVENTION
The present invention is directed to compounds, pharmaceutical
compositions, and methods of using such compounds or compositions
thereof for treating a viral infection, or for affecting viral
activity by modulating viral replication. More particularly, the
present invention relates to indole compounds or compositions and
methods for use thereof for treating or ameliorating Hepatitis C
Virus (HCV) infection or disorders or symptoms associated therewith
by inhibiting Hepatitis C viral replication.
BACKGROUND OF THE INVENTION
An estimated 170 million people worldwide are reported to be
infected with the Hepatitis C virus, the causative agent of
hepatitis C. Seventy to eighty percent of HCV infections lead to
chronic liver infection, which in turn may result in severe liver
disease, including liver fibrosis, cirrhosis, and hepatocellular
carcinoma (see Saito I, et al., Hepatitis C virus infection is
associated with the development of hepatocellular carcinoma, Proc
Natl Acad Sci USA, 2003, 87:6547-6549).
Although the treatment outcome is variable among the six major HCV
genotypes, only about one-half of all treated patients respond to
therapy, suggesting that the virus encodes protein products that
may directly or indirectly attenuate the antiviral action of
interferon (IFN). IFNs are naturally produced in response to viral
infection, and cellular exposure to IFN leads to the induced
expression of a variety of IFN-stimulated genes (ISGs), many of
which have an antiviral function. ISG action can limit virus
replication at multiple points within the replicative cycle.
Compounds and methods for treating Hepatitis C have been disclosed
in U.S. patent application Ser. No. 11/653,450, filed Jan. 16, 2007
(having corresponding International Application No.
PCT/US2007/00996, filed Jan. 16, 2007), U.S. patent application
Ser. No. 11/653,448, filed Jan. 16, 2007 (having corresponding
International Application No. PCT/US2007/00923, filed Jan. 16,
2007), each of which are a continuation-in-part of U.S. patent
application Ser. No. 11/331,180, filed Jan. 13, 2006, which is a
continuation-in-part of U.S. patent application Ser. No.
11/180,961, filed Jul. 14, 2005 (having corresponding International
Application No. PCT/US2005/024881, filed Jul. 14, 2005), each of
which are incorporated herein by reference in their entirety and
for all purposes.
United States Patent Publication 2006/0235028 discloses certain
aryl and heteroaryl compounds as 11-beta-hydroxysteroid
dehydrogenase type I inhibitors.
All other documents referred to herein are incorporated by
reference into the present application as though fully set forth
herein.
SUMMARY OF THE INVENTION
The present invention is directed to a compound of Formula (I):
##STR00001## wherein R.sub.1, R.sub.2, X, Z and Ar are as defined
herein and forms and compositions thereof, and methods of using
such compounds, forms or compositions thereof for treating a viral
infection, or for affecting viral activity by modulating viral
replication.
DETAILED DESCRIPTION OF THE INVENTION
The present invention is directed to a compound of Formula (I):
##STR00002## or a free acid, free base, salt, hydrate, solvate,
clathrate, isotopologue, racemate, enantiomer, diastereomer,
stereoisomer or polymorph form thereof, wherein X is hydrogen,
halogen, cyano, nitro, carboxyl, C.sub.1-8alkyl-carbonyl,
C.sub.1-8alkoxy-carbonyl, formyl, amino, C.sub.1-8alkyl-amino,
amino-carbonyl, C.sub.1-8alkyl-amino-carbonyl or
C.sub.1-8alkyl-sulfonyl-; Ar is heteroaryl or heterocyclyl, each
optionally substituted with one or two substituents independently
selected from halogen, C.sub.1-8alkyl, halo-C.sub.1-8alkyl,
C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy, amino or
C.sub.1-8alkyl-amino; Z is C.sub.1-8alkyl,
C.sub.2-8alkenyl-C.sub.1-8alkyl, C.sub.2-8alkynyl-C.sub.1-8alkyl,
halo-C.sub.1-8alkyl, C.sub.1-8alkoxy-C.sub.1-8alkyl,
C.sub.1-8alkoxy-carbonyl, carboxyl, C.sub.3-14cycloalkyl,
C.sub.1-14cycloalkenyl, C.sub.3-14cycloalkyl-C.sub.1-8alkyl, aryl,
aryl-C.sub.1-8 alkyl, heteroaryl, heteroaryl-C.sub.1-8alkyl,
heterocyclyl or heterocyclyl-C.sub.1-8alkyl, wherein each instance
of aryl and heteroaryl is optionally substituted with one, two,
three or four substituents each selected from hydroxy, cyano,
nitro, halogen, C.sub.1-8alkyl, C.sub.2-8alkenyl, C.sub.2-8alkynyl,
hydroxy-C.sub.1-8alkyl, halo-C.sub.1-8alkyl, C.sub.1-8alkoxy,
halo-C.sub.1-8alkoxy, amino, C.sub.1-8alkyl-amino,
C.sub.1-8alkoxy-C.sub.1-8alkyl, C.sub.1-8alkylthio,
C.sub.1-8alkyl-carbonyl, C.sub.1-8alkoxy-carbonyl,
C.sub.1-8alkyl-carbonyloxy or amino-sulfonyl; R.sub.1 is
--N(R.sub.3)--SO.sub.2--R.sub.4,
--N(R.sub.3)--SO.sub.2--N(R.sub.5)--R.sub.6,
--SO.sub.2--N(R.sub.5)--R.sub.6 or --SO.sub.2--R.sub.7; R.sub.2 is
one, two, three or four substituents each selected from hydrogen,
halogen, hydroxy, cyano, nitro, C.sub.1-8alkyl,
hydroxy-C.sub.1-8alkyl, halo-C.sub.1-8alkyl, C.sub.2-8alkenyl,
halo-C.sub.2-8alkenyl, C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy,
C.sub.1-8alkoxy-C.sub.1-8alkyl, C.sub.1-8alkyl-carbonyl,
C.sub.1-8alkoxy-carbonyl, C.sub.1-8alkyl-carbonyloxy,
C.sub.1-8alkyl-carbonyloxy-C.sub.1-8alkyl,
C.sub.1-8alkyl-carbonyloxy-C.sub.1-8alkoxy, amino,
C.sub.1-8alkyl-amino, amino-C.sub.1-8alkyl,
C.sub.1-8alkyl-amino-C.sub.1-8alkyl, amino-C.sub.1-8alkoxy,
C.sub.1-8alkyl-amino-C.sub.1-8alkoxy,
C.sub.1-8alkoxy-C.sub.1-8alkyl-amino-C.sub.1-8alkoxy,
amino-C.sub.1-8alkyl-amino-C.sub.1-8alkoxy,
C.sub.1-8alkyl-amino-C.sub.1-8alkyl-amino-C.sub.1-8alkoxy,
C.sub.1-8alkoxy-carbonyl-amino, carboxyl-amino, amino-carbonyl,
amino-carbonyl-amino, C.sub.1-8alkyl-amino-carbonyl-amino,
C.sub.1-8alkylthio, C.sub.1-8alkyl-sulfinyl,
C.sub.1-8alkyl-sulfonyl, C.sub.1-8alkyl-sulfonyl-amino,
C.sub.3-14cycloalkyl, C.sub.3-14cycloalkyl-C.sub.1-8alkyl,
C.sub.3-14cycloalkyl-C.sub.1-8alkoxy, C.sub.3-14cycloalkyloxy,
aryl, aryl-C.sub.1-8alkyl, aryl-C.sub.1-8alkoxy, aryloxy,
aryl-carbonyl-amino, heteroaryl, heteroaryl-C.sub.1-8alkyl,
heteroaryl-C.sub.1-8alkoxy, heteroaryloxy, heterocyclyl,
heterocyclyl-C.sub.1-8alkyl, heterocyclyl-C.sub.1-8alkoxy,
heterocyclyloxy or heterocyclyl-carbonyloxy, wherein each instance
of C.sub.3-14cycloalkyl, aryl, heteroaryl and heterocyclyl is
optionally substituted with one, two, three or four substituents
each selected from halogen, cyano, C.sub.1-8alkyl, C.sub.1-8alkoxy,
C.sub.1-8alkoxy-C.sub.1-8alkyl, amino, C.sub.1-8alkyl-amino,
amino-C.sub.1-8alkyl or C.sub.1-8alkyl-amino-C.sub.1-8alkyl;
R.sub.3 is hydrogen or C.sub.1-8alkyl, optionally substituted on
C.sub.1-8alkyl with one or more substituents each selected from
halogen, hydroxy, cyano, C.sub.1-8alkoxy, amino or
C.sub.1-8alkyl-amino; R.sub.4 is C.sub.1-8alkyl,
halo-C.sub.1-8alkyl, C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy,
C.sub.3-14cycloalkyl, C.sub.3-14cycloalkyl-C.sub.1-8alkyl, aryl,
aryl-C.sub.1-8alkyl, heteroaryl, heteroaryl-C.sub.1-8alkyl,
heterocyclyl or heterocyclyl-C.sub.1-8alkyl, wherein each instance
of aryl, heteroaryl, heterocyclyl and C.sub.3-14cycloalkyl is
optionally substituted with one or two substituents each selected
from halogen, C.sub.1-8alkyl, halo-C.sub.1-8alkyl, C.sub.1-8alkoxy,
halo-C.sub.1-8alkoxy, amino or C.sub.1-8alkyl-amino; R.sub.5 is
hydrogen, C.sub.1-8alkyl, C.sub.1-8alkyl-carbonyl- or
C.sub.3-14cycloalkyl, optionally substituted on C.sub.1-8alkyl with
one or more substituents each selected from halogen, hydroxy, cyano
or C.sub.1-8alkoxy; R.sub.6 is hydrogen, C.sub.1-8alkyl,
hydroxy-C.sub.1-8alkyl, halo-C.sub.1-8alkyl, cyano-C.sub.1-8alkyl,
C.sub.1-8alkoxy-C.sub.1-8alkyl, amino-C.sub.1-8alkyl,
C.sub.1-8alkyl-amino-C.sub.1-8alkyl, C.sub.1-8alkyl-carbonyl,
C.sub.1-8alkoxy-carbonyl, C.sub.3-14cycloalkyl,
C.sub.3-14cycloalkyl-C.sub.1-8alkyl, aryl, aryl-C.sub.1-8alkyl,
heteroaryl, heteroaryl-C.sub.1-8alkyl, heterocyclyl or
heterocyclyl-C.sub.1-8alkyl, wherein each instance of aryl,
heteroaryl, heterocyclyl and C.sub.3-14cycloalkyl is optionally
substituted with one or two substituents each selected from
halogen, C.sub.1-8alkyl, halo-C.sub.1-8alkyl, C.sub.1-8alkoxy,
halo-C.sub.1-8alkoxy, amino or C.sub.1-8alkyl-amino; and R.sub.7 is
C.sub.1-8alkyl, C.sub.3-14cycloalkyl,
C.sub.3-14cycloalkyl-C.sub.1-8alkyl, aryl, aryl-C.sub.1-8alkyl,
heteroaryl, heteroaryl-C.sub.1-8alkyl, heterocyclyl or
heterocyclyl-C.sub.1-8alkyl, wherein each instance of aryl,
heteroaryl, C.sub.3-14cycloalkyl and heterocyclyl is optionally
substituted with one or two substituents each selected from
halogen, C.sub.1-8alkyl, halo-C.sub.1-8alkyl, C.sub.1-8alkoxy,
halo-C.sub.1-8alkoxy, amino or C.sub.1-8alkyl-amino.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein X is selected from hydrogen, cyano,
carboxyl, amino-carbonyl or C.sub.1-8alkyl-amino-carbonyl; Ar is
heteroaryl; Z is C.sub.1-8alkyl, C.sub.3-14cycloalkyl,
C.sub.3-14cycloalkenyl, C.sub.3-14cycloalkyl-C.sub.1-8alkyl, aryl,
aryl-C.sub.1-8alkyl, heteroaryl, heteroaryl-C.sub.1-8alkyl,
heterocyclyl or heterocyclyl-C.sub.1-8alkyl, wherein each instance
of aryl and heteroaryl is optionally substituted with a substituent
selected from cyano, halogen, C.sub.1-8alkyl, C.sub.1-8alkoxy,
amino or C.sub.1-8alkyl-amino; R.sub.2 is one, two or three
substituents each selected from hydrogen, halogen, hydroxy, cyano,
C.sub.1-8alkyl, hydroxy-C.sub.1-8alkyl, halo-C.sub.1-8alkyl,
halo-C.sub.2-8alkenyl, C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy,
C.sub.1-8alkyl-carbonyl, C.sub.1-8alkoxy-carbonyl,
C.sub.1-8alkyl-carbonyloxy, amino, C.sub.1-8alkyl-amino,
amino-C.sub.1-8alkyl, C.sub.1-8alkyl-amino-C.sub.1-8alkyl,
C.sub.1-8 alkylthio, C.sub.1-8 alkyl-sulfinyl,
C.sub.1-8alkyl-sulfonyl, C.sub.3-14cycloalkyl,
C.sub.3-14cycloalkyl-C.sub.1-8alkyl,
C.sub.3-14cycloalkyl-C.sub.1-8alkoxy, C.sub.3-14cycloalkyloxy,
heteroaryl, heteroaryl-C.sub.1-8alkyl, heteroaryl-C.sub.1-8alkoxy,
heteroaryloxy, heterocyclyl, heterocyclyl-C.sub.1-8alkyl,
heterocyclyl-C.sub.1-8alkoxy or heterocyclyloxy, wherein
heteroaryloxy is optionally substituted with a cyano substituent;
R.sub.3 is hydrogen or C.sub.1-8alkyl, optionally substituted on
C.sub.1-8alkyl with one or more substituents each selected from
halogen, hydroxy or cyano; R.sub.4 is C.sub.1-8alkyl,
halo-C.sub.1-8alkyl, C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy,
C.sub.3-14cycloalkyl, C.sub.3-14cycloalkyl-C.sub.1-8alkyl, aryl,
aryl-C.sub.1-8alkyl, heteroaryl, heteroaryl-C.sub.1-8alkyl,
heterocyclyl or heterocyclyl-C.sub.1-8alkyl; R.sub.5 is hydrogen;
R.sub.6 is hydrogen, C.sub.1-8alkyl, hydroxy-C.sub.1-8alkyl,
halo-C.sub.1-8alkyl, cyano-C.sub.1-8alkyl, C.sub.3-14cycloalkyl or
C.sub.3-14cycloalkyl-C.sub.1-8alkyl, wherein each instance of
C.sub.3-14cycloalkyl is optionally substituted with one or two
substituents each selected from halogen, C.sub.1-8alkyl or
halo-C.sub.1-8alkyl; and R.sub.7 is C.sub.1-8alkyl or heterocyclyl;
and all other variables are as previously defined.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein X is cyano; Ar is pyridinyl,
pyrimidinyl or pyridazinyl; Z is C.sub.1-8alkyl, cyclopropyl,
cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl,
cyclopropyl-methyl, phenyl, thiazolyl, pyridinyl, pyrimidinyl,
pyrazinyl, pyridazinyl, triazinyl or tetrahydrofuran, wherein
phenyl is optionally substituted with a substituent selected from
cyano, halogen, C.sub.1-8alkyl or C.sub.1-8alkoxy; R.sub.2 is one,
two or three substituents each selected from hydrogen, halogen,
hydroxy, cyano, C.sub.1-8alkyl, halo-C.sub.1-8alkyl,
halo-C.sub.2-8alkenyl, C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy,
C.sub.1-8alkylthio, C.sub.1-8alkyl-sulfinyl,
C.sub.1-8alkyl-sulfonyl, cyclopropyl, cyclobutyl, cyclobutoxy,
pyridinyloxy, pyrimidinyloxy, pyrazinyloxy or morpholinyl, wherein
pyridinyl and pyrazinyl are each optionally substituted with a
cyano substituent; R.sub.3 is hydrogen, methyl, ethyl, propyl,
isopropyl or tert-butyl, wherein methyl, ethyl, propyl and
isopropyl are each optionally substituted with one or more
substituents each selected from halogen, hydroxy or cyano; R.sub.4
is C.sub.1-8alkyl or cyclopropyl; R.sub.6 is hydrogen,
C.sub.1-8alkyl, hydroxy-C.sub.1-8alkyl, halo-C.sub.1-8alkyl,
cyano-C.sub.1-8alkyl, cyclopropyl, cyclobutyl or
1-cyclopropyl-ethyl, wherein each instance of cyclopropyl and
cyclobutyl is optionally substituted with one or two substituents
each selected from halogen, C.sub.1-8alkyl or halo-C.sub.1-8alkyl;
and R.sub.7 is C.sub.1-8alkyl or piperidinyl; and all other
variables are as previously defined.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein the isotopologue is deuterium.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein R.sub.2 is C.sub.1-8alkyl wherein
from 1 to 3 hydrogen atoms are optionally replaced with deuterium;
R.sub.4 is C.sub.1-8alkyl wherein from 1 to 3 hydrogen atoms are
optionally replaced with deuterium or halo-C.sub.1-8alkyl wherein
from 1 to 3 hydrogen atoms are optionally replaced with deuterium;
R.sub.6 is C.sub.1-8alkyl wherein from 1 to 3 hydrogen atoms are
optionally replaced with deuterium or halo-C.sub.1-8alkyl wherein
from 1 to 3 hydrogen atoms are optionally replaced with deuterium;
and R.sub.7 is C.sub.1-8alkyl wherein from 1 to 3 hydrogen atoms
are optionally replaced with deuterium or halo-C.sub.1-8alkyl
wherein from 1 to 3 hydrogen atoms are optionally replaced with
deuterium.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein Z is methyl, ethyl,
2-hydroxy-ethyl-, propyl, isopropyl, tert-butyl, cyclopropyl,
cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl,
cyclopropyl-methyl, (cyclopropyl, methyl)methyl-, phenyl,
thiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl,
pyrazolyl, tetrahydro-2H-pyranyl, 1,6-dihydropyrimidinyl, thienyl,
furanyl, oxazolyl, triazinyl or tetrahydrofuran, wherein phenyl,
oxazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyrazolyl, thienyl,
furanyl, thiazoyl is optionally substituted with one, two or three
substituents each selected from chloro, cyano, nitro,
trifluoromethyl, methyl-carbonyl-, methoxy-carbonyl,
amino-sulfonyl-, hydroxymethyl-, fluoro, methyl or methoxy; R.sub.2
is one, two or three substituents each selected from hydrogen,
chloro, fluoro, bromo, hydroxy, cyano, methyl, ethyl, isopropyl,
fluoromethyl, difluoromethyl, trifluoromethyl, difluoroethyl,
difluoroethenyl, ethoxy, methoxy, isopropoxy, difluoromethoxy,
trifluoromethoxy, difluoroethoxy, trifluoroethoxy, methylthio,
isopropylthio, 1-hydroxy-ethyl-, 2-methyl-1,3-dioxolanyl, propenyl,
cyclopropyl, cyclobutyl, cyclobutoxy, pyridinyloxy, pyrimidinyloxy,
pyrazinyloxy, vinyl, methyl-carbonyl-, or morpholinyl, wherein
pyridinyl and pyrazinyl are each optionally substituted with a
cyano substituent; R.sub.4 is methyl, ethyl, propyl, isopropyl,
tert-butyl or cyclopropyl; R.sub.6 is hydrogen, methyl, ethyl,
propyl, isopropyl, tert-butyl, dihydroxyisopropyl,
difluoroisopropyl, trifluoroisopropyl, fluoro-tert-butyl,
trifluoro-tert-butyl, cyano-methyl, 1-cyano-ethyl, cyclopropyl,
cyclobutyl or 1-cyclopropyl-ethyl, wherein each instance of
cyclopropyl and cyclobutyl is optionally substituted with one or
two substituents each selected from fluoro, methyl or
trifluoromethyl; R.sub.7 is methyl, ethyl, propyl, isopropyl,
tert-butyl or piperidinyl; and all other variables are as
previously defined.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein X is selected from hydrogen, chloro,
cyano, amino-carbonyl, methoxy-carbonyl-, carboxyl-,
methyl-amino-carbonyl, ethyl-amino-carbonyl,
isopropyl-amino-carbonyl, dimethyl-amino-carbonyl, methyl-sulfonyl
or methyl-carbonyl.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein X is cyano.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein Ar is heteroaryl or
heterocyclyl.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein Ar is heteroaryl.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein Ar is pyridinyl, pyrimidinyl or
pyridazinyl.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein Z is C.sub.1-8alkyl,
C.sub.3-14cycloalkyl, C.sub.3-14cycloalkenyl,
C.sub.3-14cycloalkyl-C.sub.1-8alkyl, aryl, aryl-C.sub.1-8alkyl,
heteroaryl, heteroaryl-C.sub.1-8alkyl, heterocyclyl or
heterocyclyl-C.sub.1-8alkyl, wherein each instance of aryl and
heteroaryl is optionally substituted with a substituent selected
from cyano, halogen, C.sub.1-8alkyl, C.sub.1-8alkoxy, amino or
C.sub.1-8alkyl-amino.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein Z is C.sub.1-8alkyl, cyclopropyl,
cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl,
cyclopropyl-methyl, (cyclopropyl, methyl)methyl-, phenyl,
thiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl,
pyrazolyl, tetrahydro-2H-pyranyl, 1,6-dihydropyrimidinyl, thienyl,
furanyl, oxazolyl, triazinyl or tetrahydrofuran, wherein phenyl,
oxazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyrazolyl, thienyl,
furanyl, thiazoyl is optionally substituted with one, two or three
substituents each selected from chloro, cyano, nitro,
halo-C.sub.1-8alkyl, C.sub.1-8alkyl-carbonyl-,
C.sub.1-8alkoxy-carbonyl, amino-sulfonyl, hydroxyl-C.sub.1-8alkyl-,
cyano, halogen, C.sub.1-8alkyl or C.sub.1-8alkoxy.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein Z is methyl, ethyl,
2-hydroxy-ethyl-, propyl, isopropyl, tert-butyl, cyclopropyl,
cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl,
cyclopropyl-methyl, (cyclopropyl, methyl)methyl-, phenyl,
thiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl,
pyrazolyl, tetrahydro-2H-pyranyl, 1,6-dihydropyrimidinyl, thienyl,
furanyl, oxazolyl, triazinyl or tetrahydrofuran, wherein phenyl,
oxazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyrazolyl, thienyl,
furanyl, thiazoyl is optionally substituted with one, two or three
substituents each selected from chloro, nitro, trifluoromethyl,
methyl-carbonyl-, methoxy-carbonyl, amino-sulfonyl, hydroxymethyl-,
cyano, fluoro, methyl or methoxy.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein R.sub.2 is one, two or three
substituents each selected from hydrogen, halogen, hydroxy, cyano,
C.sub.1-8alkyl, hydroxy-C.sub.1-8alkyl, halo-C.sub.1-8alkyl,
halo-C.sub.2-8alkenyl, C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy,
C.sub.1-8alkyl-carbonyl, C.sub.1-8alkoxy-carbonyl,
C.sub.1-8alkyl-carbonyloxy, amino, C.sub.1-8alkyl-amino,
amino-C.sub.1-8alkyl, C.sub.1-8alkyl-amino-C.sub.1-8alkyl,
C.sub.1-8alkylthio, C.sub.1-8alkyl-sulfinyl, C.sub.1-8alkyl
sulfonyl, C.sub.3-14cycloalkyl,
C.sub.3-14cycloalkyl-C.sub.1-8alkyl,
C.sub.3-14cycloalkyl-C.sub.1-8alkoxy, C.sub.3-14cycloalkyloxy,
heteroaryl, heteroaryl-C.sub.1-8alkyl, heteroaryl-C.sub.1-8alkoxy,
heteroaryloxy, heterocyclyl, heterocyclyl-C.sub.1-8alkyl,
heterocyclyl-C.sub.1-8alkoxy or heterocyclyloxy, wherein
heteroaryloxy is optionally substituted with a cyano
substituent.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein R.sub.2 is one, two or three
substituents each selected from hydrogen, halogen, hydroxy, cyano,
C.sub.1-8alkyl, halo-C.sub.1-8alkyl, halo-C.sub.2-8alkenyl,
C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy, C.sub.1-8alkylthio,
C.sub.1-8alkyl-sulfinyl, C.sub.1-8alkyl-sulfonyl,
C.sub.3-14cycloalkyl, C.sub.3-14cycloalkyloxy, heteroaryloxy or
heterocyclyl, wherein heteroaryloxy is optionally substituted with
a cyano substituent.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein R.sub.2 is one, two or three
substituents each selected from hydrogen, chloro, fluoro, bromo,
hydroxy, cyano, methyl, ethyl, isopropyl, fluoromethyl,
difluoromethyl, trifluoromethyl, difluoroethyl, difluoroethenyl,
ethoxy, methoxy, isopropoxy, difluoromethoxy, trifluoromethoxy,
difluoroethoxy, trifluoroethoxy, methylthio, isopropylthio,
1-hydroxy-ethyl-, 2-methyl-1,3-dioxolanyl, propenyl, cyclopropyl,
cyclobutyl, cyclobutoxy, pyridinyloxy, pyrimidinyloxy, pyrazinyloxy
vinyl, methyl-carbonyl-, or morpholinyl, wherein pyridinyl and
pyrazinyl are each optionally substituted with a cyano
substituent.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein R.sub.3 is hydrogen or
C.sub.1-8alkyl, optionally substituted on C.sub.1-8alkyl with one
or more substituents each selected from halogen, hydroxy or
cyano.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein R.sub.3 is hydrogen, methyl, ethyl,
propyl, isopropyl or tert-butyl, wherein methyl and ethyl are each
optionally substituted with one or more substituents each selected
from halogen, hydroxy or cyano.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein R.sub.4 is C.sub.1-8alkyl,
halo-C.sub.1-8alkyl, C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy,
C.sub.3-14cycloalkyl, C.sub.3-14cycloalkyl-C.sub.1-8alkyl, aryl,
aryl-C.sub.1-8alkyl, heteroaryl, heteroaryl-C.sub.1-8alkyl,
heterocyclyl or heterocyclyl-C.sub.1-8alkyl.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein R.sub.4 is C.sub.1-8alkyl or
C.sub.3-14cycloalkyl.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein R.sub.4 is C.sub.1-8alkyl or
cyclopropyl.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein R.sub.4 is methyl, ethyl, propyl,
isopropyl, tert-butyl or cyclopropyl.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein R.sub.5 is hydrogen.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein R.sub.6 is hydrogen, C.sub.1-8alkyl,
hydroxy-C.sub.1-8alkyl, halo-C.sub.1-8alkyl, cyano-C.sub.1-8alkyl,
C.sub.3-14cycloalkyl, C.sub.3-14cycloalkyl-C.sub.1-8alkyl, aryl,
aryl-C.sub.1-8alkyl, heteroaryl, heteroaryl-C.sub.1-8alkyl,
heterocyclyl or heterocyclyl-C.sub.1-8alkyl, wherein each instance
of aryl, heteroaryl, heterocyclyl and C.sub.3-14cycloalkyl is
optionally substituted with one or two substituents each selected
from halogen, C.sub.1-8alkyl, halo-C.sub.1-8alkyl, C.sub.1-8alkoxy,
halo-C.sub.1-8alkoxy, amino or C.sub.1-8alkyl-amino.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein R.sub.6 is hydrogen, C.sub.1-8alkyl,
hydroxy-C.sub.1-8alkyl, halo-C.sub.1-8alkyl, cyano-C.sub.1-8alkyl,
C.sub.3-14cycloalkyl or C.sub.3-14cycloalkyl-C.sub.1-8alkyl,
wherein each instance of C.sub.3-14cycloalkyl is optionally
substituted with one or two substituents each selected from
halogen, C.sub.1-8alkyl or halo-C.sub.1-8alkyl.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein R.sub.6 is hydrogen, methyl, ethyl,
propyl, isopropyl, tert-butyl, dihydroxyisopropyl,
difluoroisopropyl, trifluoroisopropyl, fluoro-tert-butyl,
trifluoro-tert-butyl, cyano-methyl, 1-cyano-ethyl, cyclopropyl,
cyclobutyl, cyclobutyl-methyl-, 1-(trifluoromethyl)ethyl-,
1-(trifluoromethyl)isopropyl, 1-(trifluoromethyl)propyl,
pyrimidinyl, phenyl or 1-cyclopropyl-ethyl, wherein each instance
of cyclopropyl and cyclobutyl is optionally substituted with one or
two substituents each selected from fluoro, methyl or
trifluoromethyl.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein R.sub.7 is C.sub.1-8alkyl or
heterocyclyl.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein R.sub.7 is C.sub.1-8alkyl or
piperidinyl.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein R.sub.7 is methyl, ethyl, propyl,
isopropyl, tert-butyl or piperidinyl.
Embodiments of the present invention include a compound of Formula
(I) and forms thereof, wherein R.sub.7 is piperidinyl.
Embodiments of the present invention include a compound of Formula
(I), selected from a compound of Formula (Ia):
##STR00003## or a free acid, free base, salt, hydrate, solvate,
clathrate, isotopologue, racemate, enantiomer, diastereomer,
stereoisomer or polymorph form thereof, wherein R.sub.8 is
hydrogen, halogen or C.sub.1-8alkoxy; R.sub.9 is hydrogen, halogen,
hydroxy, cyano, nitro, C.sub.1-8alkyl, halo-C.sub.1-8alkyl,
C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy, C.sub.1-8alkyl-carbonyl,
C.sub.1-8alkoxy-carbonyl, amino, C.sub.1-8alkyl-amino,
amino-C.sub.1-8alkyl, C.sub.1-8alkyl-amino-C.sub.1-8alkyl,
C.sub.1-8alkylthio, C.sub.3-14cycloalkyl,
C.sub.3-14cycloalkyl-C.sub.1-8alkoxy, aryl, aryl-C.sub.1-8alkoxy,
heteroaryl, heteroaryl-C.sub.1-8alkoxy, heterocyclyl or
heterocyclyl-C.sub.1-8alkoxy, wherein each instance of
C.sub.3-14cycloalkyl, aryl, heteroaryl and heterocyclyl is
optionally substituted with one, two, three or four substituents
each selected from halogen, cyano, C.sub.1-8alkyl, C.sub.1-8alkoxy,
C.sub.1-8alkoxy-C.sub.1-8alkyl, amino, C.sub.1-8alkyl-amino,
amino-C.sub.1-8alkyl or C.sub.1-8alkyl-amino-C.sub.1-8alkyl;
R.sub.10 is hydrogen, halogen, hydroxy, cyano, nitro,
C.sub.1-8alkyl, halo-C.sub.1-8alkyl, C.sub.2-8alkenyl,
halo-C.sub.2-8alkenyl, hydroxy-C.sub.1-8alkyl, C.sub.1-8alkoxy,
halo-C.sub.1-8alkoxy, C.sub.1-8alkoxy-C.sub.1-8alkyl,
C.sub.1-8alkyl-carbonyl, C.sub.1-8alkoxy-carbonyl,
C.sub.1-8alkyl-carbonyloxy,
C.sub.1-8alkyl-carbonyloxy-C.sub.1-8alkoxy, amino,
C.sub.1-8alkyl-amino, amino-C.sub.1-8alkyl,
C.sub.1-8alkyl-amino-C.sub.1-8alkyl, amino-C.sub.1-8alkoxy,
C.sub.1-8alkyl-amino-C.sub.1-8alkoxy,
C.sub.1-8alkoxy-C.sub.1-8alkyl-amino-C.sub.1-8alkoxy,
amino-C.sub.1-8alkyl-amino-C.sub.1-8alkoxy,
C.sub.1-8alkyl-amino-C.sub.1-8alkyl-amino-C.sub.1-8alkoxy,
C.sub.1-8alkoxy-carbonyl-amino, carboxyl-amino, amino-carbonyl,
amino-carbonyl-amino, C.sub.1-8alkyl-amino-carbonyl-amino,
C.sub.1-8alkylthio, C.sub.1-8alkyl-sulfinyl,
C.sub.1-8alkyl-sulfonyl, C.sub.1-8alkyl-sulfonyl-amino,
C.sub.3-14cycloalkyl, C.sub.3-14cycloalkyl-C.sub.1-8alkoxy,
C.sub.3-14cycloalkyl-C.sub.1-8alkoxy, C.sub.3-14cycloalkyloxy,
aryl, aryl-C.sub.1-8alkyl, aryl-C.sub.1-8alkoxy, aryloxy,
aryl-carbonyl-amino, heteroaryl, heteroaryl-C.sub.1-8alkyl,
heteroaryl-C.sub.1-8alkoxy, heteroaryloxy, heterocyclyl,
heterocyclyl-C.sub.1-8alkyl, heterocyclyl-C.sub.1-8alkoxy,
heterocyclyloxy or heterocyclyl-carbonyloxy, wherein each instance
of C.sub.3-14cycloalkyl, aryl, heteroaryl and heterocyclyl is
optionally substituted with one, two, three or four substituents
each selected from halogen, cyano, C.sub.1-8alkyl, C.sub.1-8alkoxy,
C.sub.1-8alkoxy-C.sub.1-8alkyl, amino, C.sub.1-8alkyl-amino,
amino-C.sub.1-8alkyl or C.sub.1-8alkyl-amino-C.sub.1-8alkyl; and
R.sub.11 is hydrogen, halogen, hydroxy, cyano, nitro,
C.sub.1-8alkyl, halo-C.sub.1-8alkyl, C.sub.1-8alkoxy,
halo-C.sub.1-8alkoxy, C.sub.1-8alkyl-carbonyl,
C.sub.1-8alkoxy-carbonyl, C.sub.1-8alkyl-carbonyloxy or
C.sub.1-8alkyl-carbonyloxy-C.sub.1-8alkyl; and all other variables
are as previously defined.
Embodiments of the present invention include a compound of Formula
(Ia) and forms thereof, wherein R.sub.8 is hydrogen or halogen;
R.sub.9 is hydrogen, halogen, hydroxy, cyano, C.sub.1-8alkyl,
halo-C.sub.1-8alkyl, C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy,
C.sub.1-8alkylthio or C.sub.3-14cycloalkyl; R.sub.10 is hydrogen,
halogen, hydroxy, cyano, C.sub.1-8alkyl, halo-C.sub.1-8alkyl,
halo-C.sub.2-8alkenyl, C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy,
C.sub.1-8alkylthio, C.sub.3-14cycloalkyl, C.sub.3-14cycloalkyloxy,
heteroaryloxy or heterocyclyl, wherein heteroaryloxy is optionally
substituted with a cyano substituent; and R.sub.11 is hydrogen or
halogen; and all other variables are as previously defined.
Embodiments of the present invention include a compound of Formula
(Ia) and forms thereof, wherein R.sub.9 is hydrogen, halogen,
hydroxy, cyano, C.sub.1-8alkyl, halo-C.sub.1-8alkyl,
C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy, C.sub.1-8alkylthio or
cyclopropyl; and R.sub.10 is hydrogen, halogen, hydroxy, cyano,
C.sub.1-8alkyl, halo-C.sub.1-8alkyl, halo-C.sub.2-8alkenyl,
C.sub.1-8alkoxy, halo-C.sub.1-8alkoxy, C.sub.1-8alkylthio,
cyclopropyl, cyclobutyl, cyclobutoxy, pyridinyloxy, pyrimidinyloxy,
pyrazinyloxy or morpholinyl, wherein pyridinyl and pyrazinyl are
optionally substituted with a cyano substituent; and all other
variables are as previously defined.
Embodiments of the present invention include a compound of Formula
(Ia) and forms thereof, wherein R.sub.8 is hydrogen, fluoro or
methoxy; R.sub.9 is hydrogen, chloro, fluoro, bromo, hydroxy,
cyano, methyl, ethyl, fluoromethyl, difluoromethyl, difluoroethyl,
methoxy, difluoromethoxy, trifluoromethoxy, methylthio or
cyclopropyl; R.sub.10 is hydrogen, bromo, chloro, fluoro, hydroxy,
cyano, methyl, ethyl, isopropyl, fluoromethyl, difluoromethyl,
difluoroethyl, difluoroethenyl, methoxy, ethoxy, isopropoxy,
difluoromethoxy, trifluoromethoxy, fluoroethoxy, difluoroethoxy,
trifluoroethoxy, methylthio, isopropylthio, methyl-carbonyl, vinyl,
propenyl, 1-hydroxy-ethyl, 2-methyl-1,3-dioxolanyl, propenyl,
cyclopropyl, cyclobutyl, cyclobutoxy, pyridinyloxy, pyrimidinyloxy,
pyrazinyloxy or morpholinyl, wherein pyridinyl and pyrazinyl are
optionally substituted with a cyano substituent; and R.sub.11 is
hydrogen, chloro, fluoro or methyl; and all other variables are as
previously defined.
In one embodiment of the present invention, a compound of Formula
(I) or a free acid, free base, salt, hydrate, solvate, clathrate,
isotopologue, racemate, enantiomer, diastereomer, stereoisomer or
polymorph form thereof is selected from:
##STR00004## ##STR00005## ##STR00006## ##STR00007## ##STR00008##
##STR00009## ##STR00010## ##STR00011## ##STR00012## ##STR00013##
##STR00014## ##STR00015## ##STR00016## ##STR00017## ##STR00018##
##STR00019## ##STR00020## ##STR00021## ##STR00022## ##STR00023##
##STR00024## ##STR00025## ##STR00026## ##STR00027## ##STR00028##
##STR00029## ##STR00030## ##STR00031## ##STR00032## ##STR00033##
##STR00034## ##STR00035## ##STR00036## ##STR00037## ##STR00038##
##STR00039## ##STR00040## ##STR00041## ##STR00042## ##STR00043##
##STR00044## ##STR00045## ##STR00046## ##STR00047## ##STR00048##
##STR00049## ##STR00050## ##STR00051## ##STR00052## ##STR00053##
##STR00054## ##STR00055## ##STR00056## ##STR00057## ##STR00058##
##STR00059## ##STR00060## ##STR00061## ##STR00062## ##STR00063##
##STR00064## ##STR00065## ##STR00066## ##STR00067## ##STR00068##
##STR00069## ##STR00070## ##STR00071## ##STR00072## ##STR00073##
##STR00074## ##STR00075## ##STR00076## ##STR00077## ##STR00078##
##STR00079## ##STR00080## ##STR00081## ##STR00082## ##STR00083##
##STR00084## ##STR00085## ##STR00086## ##STR00087## ##STR00088##
##STR00089## ##STR00090## ##STR00091## ##STR00092## ##STR00093##
##STR00094## ##STR00095## ##STR00096## ##STR00097## ##STR00098##
##STR00099## ##STR00100## ##STR00101## ##STR00102## ##STR00103##
##STR00104## ##STR00105## ##STR00106## ##STR00107## ##STR00108##
##STR00109## ##STR00110## ##STR00111## ##STR00112## ##STR00113##
##STR00114## ##STR00115## ##STR00116## ##STR00117## ##STR00118##
##STR00119## ##STR00120## ##STR00121## ##STR00122## ##STR00123##
##STR00124## ##STR00125## ##STR00126## ##STR00127## ##STR00128##
##STR00129## ##STR00130## ##STR00131## ##STR00132## ##STR00133##
##STR00134## ##STR00135## ##STR00136## ##STR00137## ##STR00138##
##STR00139## ##STR00140## ##STR00141## ##STR00142## ##STR00143##
##STR00144## ##STR00145## ##STR00146## ##STR00147## ##STR00148##
##STR00149## ##STR00150## ##STR00151## ##STR00152## ##STR00153##
##STR00154## ##STR00155## ##STR00156## ##STR00157## ##STR00158##
##STR00159## ##STR00160## ##STR00161## ##STR00162## ##STR00163##
##STR00164## ##STR00165## ##STR00166## ##STR00167## ##STR00168##
##STR00169## ##STR00170## ##STR00171## ##STR00172## ##STR00173##
##STR00174## ##STR00175## ##STR00176## ##STR00177## ##STR00178##
##STR00179## ##STR00180## ##STR00181## ##STR00182## ##STR00183##
##STR00184## ##STR00185## ##STR00186## ##STR00187## ##STR00188##
##STR00189## ##STR00190## ##STR00191## ##STR00192##
In another embodiment of the present invention, a compound of
Formula (I) or a free acid, free base, salt, hydrate, solvate,
clathrate, isotopologue, racemate, enantiomer, diastereomer,
stereoisomer or polymorph form thereof is selected from:
TABLE-US-00001 Cpd Name 1
6-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-yl]-N-
(propan-2-yl)pyridine-3-sulfonamide, 2
6-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-yl]-N-
cyclobutylpyridine-3-sulfonamide, 3
6-[3-cyano-6-(difluoromethoxy)-1-propyl-1H-indol-2-yl]-N-(propan-2-
yl)pyridine-3-sulfonamide, 4
5-[3-cyano-1-cyclobutyl-6-(cyclobutyloxy)-1H-indol-2-yl]-N-(propan-2-
yl)pyridine-2-sulfonamide, 5
6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-(propan-2-
yl)pyridine-3-sulfonamide, 6
6-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]-N-(propan-2-
yl)pyridine-3-sulfonamide, 7
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-(propan-2-yl)pyri-
dine-3- sulfonamide, 8
6-(3-cyano-1-cyclobutyl-5-cyclopropyl-1H-indol-2-yl)-N-(propan-2-yl)pyri-
dine-3- sulfonamide, 9
N-tert-butyl-6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)pyridine-3-
sulfonamide, 10
6-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(propan-
2-yl)pyridine-3-sulfonamide, 11
6-[3-cyano-1-(cyclopropylmethyl)-6-(trifluoromethoxy)-1H-indol-2-yl]-
N-(propan-2-yl)pyridine-3-sulfonamide, 12
6-[3-cyano-1-(propan-2-yl)-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(propa-
n- 2-yl)pyridine-3-sulfonamide, 13
6-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-1H-indol-2-yl]-
N-(propan-2-yl)pyridine-3-sulfonamide, 14
6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(propan-2-
yl)pyridine-3-sulfonamide, 15
N-tert-butyl-6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)pyridine-3--
sulfonamide, 16
6-[3-cyano-1-cyclobutyl-6-(propan-2-ylsulfanyl)-1H-indol-2-yl]-N-
(propan-2-yl)pyridine-3-sulfonamide, 17
6-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-
(propan-2-yl)pyridine-3-sulfonamide, 18
N-tert-butyl-6-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol-2-
yl]pyridine-3-sulfonamide, 19
6-[3-cyano-1-cyclobutyl-5-(difluoromethoxy)-1H-indol-2-yl]-N-(propan-
2-yl)pyridine-3-sulfonamide, 20
N-tert-butyl-6-[3-cyano-1-cyclobutyl-5-(difluoromethoxy)-1H-indol-2-
yl]pyridine-3-sulfonamide, 21
6-[3-cyano-1-cyclopentyl-5-(difluoromethoxy)-1H-indol-2-yl]-N-(propan-2-
- yl)pyridine-3-sulfonamide, 22
1-cyclobutyl-2-[5-(piperidin-1-ylsulfonyl)pyridin-2-yl]-6-(propan-2-
ylsulfanyl)-1H-indole-3-carbonitrile, 23
6-[3-cyano-1-cyclobutyl-5-(trifluoromethoxy)-1H-indol-2-yl]-N-(propan-
2-yl)pyridine-3-sulfonamide, 24
6-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 25
6-[3-cyano-1-cyclobutyl-5-(trifluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 26
5-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(propan-
2-yl)pyridine-2-sulfonamide, 27
5-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-(propan-2-
yl)pyridine-2-sulfonamide, 28
5-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(propan-2-
yl)pyridine-2-sulfonamide, 29
6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan-
2-yl)pyridine-3-sulfonamide, 30
6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(1,3-difluoropropan-
2-yl)pyridine-3-sulfonamide, 31
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 32
6-[3-cyano-1-cyclobutyl-5-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 33
6-[3-cyano-1-cyclopentyl-5-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 34
6-[3-cyano-1-cyclopentyl-5-(trifluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 35
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-(1,3-difluoropro-
pan- 2-yl)pyridine-3-sulfonamide, 36
6-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 37
6-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(1,3-difluoropropan-
2-yl)pyridine-3-sulfonamide, 38
6-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 39
5-[3-cyano-1-cyclopropyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-
(propan-2-yl)pyridine-2-sulfonamide, 40
5-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-1H-indol-2-yl]-
N-(propan-2-yl)pyridine-2-sulfonamide, 41
6-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-1H-indol-2-yl]-
N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide, 42
6-[3-cyano-1-cyclopropyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 43
6-[3-cyano-1-cyclobutyl-6-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 44
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 45
6-[3-cyano-6-(difluoromethoxy)-1-propyl-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 46
6-[3-cyano-5-fluoro-1-(tetrahydrofuran-3-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 47
6-[3-cyano-5-fluoro-1-(tetrahydrofuran-3-yl)-1H-indol-2-yl]-N-(propan-
2-yl)pyridine-3-sulfonamide, 48
6-(3-cyano-1-cyclobutyl-6-ethyl-1H-indol-2-yl)-N-(1,3-difluoropropan-
2-yl)pyridine-3-sulfonamide, 49
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 50
6-(6-chloro-3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 51
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(propan-
2-yl)pyridine-3-sulfonamide, 52
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-
(propan-2-yl)pyridine-3-sulfonamide, 53
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,1,1-
trifluoropropan-2-yl)pyridine-3-sulfonamide, 54
6-{3-cyano-6-methyl-1-[(3R)-tetrahydrofuran-3-yl]-1H-indol-2-yl}-N-
(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide, 55
6-{3-cyano-6-methyl-1-[(3R)-tetrahydrofuran-3-yl]-1H-indol-2-yl}-N-
(propan-2-yl)pyridine-3-sulfonamide, 56
6-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan-
2-yl)pyridine-3-sulfonamide, 57
6-[3-cyano-1-(cyclopropylmethyl)-6-fluoro-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 58
6-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 59
6-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethoxy)-1H-indol-2-yl]-N-
(propan-2-yl)pyridine-3-sulfonamide, 60
6-[3-cyano-5-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropa-
n- 2-yl)pyridine-3-sulfonamide, 61
6-[3-cyano-6-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropa-
n- 2-yl)pyridine-3-sulfonamide, 62
6-[6-chloro-3-cyano-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 63
6-[6-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 64
6-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 65
6-[5-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 66
6-(3-cyano-1-cyclopentyl-7-fluoro-1H-indol-2-yl)-N-(propan-2-
yl)pyridine-3-sulfonamide, 67
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1-
fluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 68
6-[3-cyano-1-(cyclopropylmethyl)-6-(trifluoromethoxy)-1H-indol-2-yl]-
N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide, 69
6-[3-cyano-1-(propan-2-yl)-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 70
6-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 71
2-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 72
6-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 73
6-[5-chloro-3-cyano-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 74
2-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 75
6-[3-cyano-6-ethyl-1-(propan-2-yl)-1H-indol-2-yl]-N-(propan-2-
yl)pyridine-3-sulfonamide, 77
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1-fluoro--
2-methylpropan-2-yl)pyridine-3-sulfonamide, 78
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,1,1-
trifluoropropan-2-yl)pyridine-3-sulfonamide, 79
6-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-(1,3-difluoropropan-
2-yl)pyridine-3-sulfonamide, 80
6-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 81
6-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 82
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 83
6-[3-cyano-6-cyclopropyl-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 84
6-[3-cyano-6-cyclopropyl-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 85
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 86
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-(1,1,1-
trifluoropropan-2-yl)pyridine-3-sulfonamide, 87
6-(3-cyano-1-cyclopentyl-7-fluoro-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 88
6-(7-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 89
6-(6-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 90
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)pyridine-3-
sulfonamide, 92
6-(3-cyano-1-cyclohexyl-6-cyclopropyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 93
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 94
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 95
6-(3-cyano-6-cyclopropyl-1-phenyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 96
6-[3-cyano-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 97
2-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 98
2-(3-cyano-1-cyclohexyl-6-methyl-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 99
6-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(propan-
2-yl)pyridine-3-sulfonamide, 100
6-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 101
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methoxy-1H-indol-2-yl)-N-(propan-
2-yl)pyridine-3-sulfonamide, 102
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methoxy-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 103
6-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethenyl)-1H-indol-2-yl]-N-(1,3--
difluoropropan-2-yl)pyridine-3-sulfonamide, 104
6-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan--
2-yl)pyridine-3-sulfonamide, 105
6-[3-cyano-1-cyclohexyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 106
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[1-
(trifluoromethyl)cyclobutyl]pyridine-3-sulfonamide, 107
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-5-fluoro-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 108
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 109
6-(3-cyano-1,6-dicyclopropyl-1H-indol-2-yl)-N-(propan-2-yl)pyridine-3--
sulfonamide, 110
6-[6-chloro-3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]-N-
(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide, 111
6-(3-cyano-6-methyl-1-phenyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-
yl)pyridine-3-sulfonamide, 112
6-(5-chloro-3-cyano-1-phenyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-
yl)pyridine-3-sulfonamide, 113
6-(3-cyano-5-fluoro-1-phenyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-
yl)pyridine-3-sulfonamide, 114
2-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 115
2-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 116
2-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(propan--
2-yl)pyrimidine-5-sulfonamide, 117
2-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-
(propan-2-yl)pyrimidine-5-sulfonamide, 118
6-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 119
6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 120
2-[5-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 121
2-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 122
2-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 123
2-[3-cyano-5-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 124
2-[3-cyano-6-cyclopropyl-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-
(propan-2-yl)pyrimidine-5-sulfonamide, 125
2-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 126
2-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 127
2-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(propan-
2-yl)pyrimidine-5-sulfonamide, 128
2-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,1,1-
trifluoropropan-2-yl)pyrimidine-5-sulfonamide, 129
2-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 130
2-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 131
2-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 132
2-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(1,3-difluoropropan--
2-yl)pyrimidine-5-sulfonamide, 133
2-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 134
2-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 135
2-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 136
2-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-1H-indol-2-yl]-
N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide, 137
2-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 138
2-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 139
2-[3-cyano-1-(cyclopropylmethyl)-6-fluoro-1H-indol-2-yl]-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 140
2-[3-cyano-6-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 141
2-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 142
6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 143
6-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 144
6-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 145
2-(3-cyano-1-cyclobutyl-6-cyclopropyl-5-fluoro-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 146
2-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 147
6-(3-cyano-1,6-dicyclopropyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-
yl)pyridine-3-sulfonamide, 148
2-(3-cyano-1,6-dicyclopropyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-
yl)pyrimidine-5-sulfonamide, 149
2-(6-chloro-3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 150
2-(3-cyano-1-cyclobutyl-5-fluoro-6-methoxy-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 151
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 152
6-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(1S)-1--
cyclopropylethyl]pyridine-3-sulfonamide, 153
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 154
6-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 155
6-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 156
2-[6-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 157
2-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3-difluoropropan-
- 2-yl)pyrimidine-5-sulfonamide, 158
6-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-(1,3-difluoropropan-
- 2-yl)pyridine-3-sulfonamide, 159
2-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 160
2-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 161
6-[3-cyano-1-cyclobutyl-6-(methylsulfanyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 162
2-[3-cyano-1-cyclobutyl-6-(methylsulfanyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 163
2-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan--
2-yl)pyrimidine-5-sulfonamide, 164
2-[3-cyano-1-(cyclopropylmethyl)-6-fluoro-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 165
2-[3-cyano-6-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 166
2-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 167
2-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 168
2-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl]-N-(propan-
2-yl)pyrimidine-5-sulfonamide, 169
2-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 170
2-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-1H-indol-2-yl]-
N-(propan-2-yl)pyrimidine-5-sulfonamide, 171
2-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-yl]-N-
(propan-2-yl)pyrimidine-5-sulfonamide, 172
2-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 173
2-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 174
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(1S)-1--
cyclopropylethyl]pyridine-3-sulfonamide, 175
2-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(1,3-difluoropropan--
2-yl)pyrimidine-5-sulfonamide, 176
2-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(1,3-difluoropropan--
2-yl)pyrimidine-5-sulfonamide, 177
2-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 178
2-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 179
2-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 180
2-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 181
2-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 182
2-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 183
2-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 184
2-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 185
2-[3-cyano-1-cyclobutyl-6-(propan-2-yl)-1H-indol-2-yl]-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 186
2-[3-cyano-1-cyclobutyl-6-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 187
2-[5-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 188
2-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3-difluoropropan-
- 2-yl)pyrimidine-5-sulfonamide, 189
2-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 190
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 191
6-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 192
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 193
2-(3-cyano-1-cyclohexyl-6-cyclopropyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 194
6-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2R)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 195
6-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 196
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 197
6-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl]-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 198
2-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 199
6-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-(1,3-difluoropropan--
2-yl)pyridine-3-sulfonamide, 200
2-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 201
6-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 202
2-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 203
2-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 204
2-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 205
2-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 206
2-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 207
2-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-yl]-N-[(1S)--
1-cyclopropylethyl]pyrimidine-5-sulfonamide, 208
2-[3-cyano-6-(difluoromethoxy)-1-propyl-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 209
2-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(1S)-1--
cyclopropylethyl]pyrimidine-5-sulfonamide, 210
6-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 211
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 212
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 213
6-(3-cyano-1-cyclohexyl-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 214
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 215
6-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 216
6-[3-cyano-1-(cyclopropylmethyl)-6-fluoro-1H-indol-2-yl]-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 217
6-(3-cyano-6-fluoro-1-propyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 218
6-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 219
6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 220
6-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 221
2-[5-chloro-3-cyano-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 222
6-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 223
6-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 224
6-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 225
6-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-6-methoxy-1H-indol-2-yl]-N-(-
1,3- difluoropropan-2-yl)pyridine-3-sulfonamide, 226
6-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 227
6-[3-cyano-6-(difluoromethoxy)-1-(2-fluorophenyl)-1H-indol-2-yl]-N-
(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide, 228
6-[3-cyano-6-(difluoromethoxy)-1-(4-fluorophenyl)-1H-indol-2-yl]-N-
(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide, 229
6-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 230
2-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 231
2-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 232
2-[3-cyano-6-(difluoromethoxy)-1-propyl-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 233
2-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 234
6-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan--
2-yl)pyridine-3-sulfonamide, 235
2-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan--
2-yl)pyrimidine-5-sulfonamide, 236
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide,
237
6-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 238
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 239
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-
dihydroxypropan-2-yl)pyridine-3-sulfonamide, 240
2-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 241
2-(3-cyano-1-cyclohexyl-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 242
2-[3-cyano-5-(difluoromethoxy)-1-ethyl-1H-indol-2-yl]-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 243
6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(3,3-
difluorocyclobutyl)pyridine-3-sulfonamide, 244
6-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(3,3-
difluorocyclobutyl)pyridine-3-sulfonamide, 245
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(3,3-
difluorocyclobutyl)pyridine-3-sulfonamide, 246
6-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N-(3,3-
difluorocyclobutyl)pyridine-3-sulfonamide, 247
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-(3,3-
difluorocyclobutyl)pyridine-3-sulfonamide, 248
6-[3-cyano-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 249
6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3--
difluoropropan-2-yl)pyridine-3-sulfonamide, 250
6-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 251
2-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 252
6-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 253
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclobutyl]pyridine-3-sulfonamide, 254
2-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 255
6-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl]-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 256
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 257
2-[6-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoroprop-
an- 2-yl)pyrimidine-5-sulfonamide, 258
6-(3-cyano-1-cyclobutyl-5-ethyl-1H-indol-2-yl)-N-(1,3-difluoropropan-
2-yl)pyridine-3-sulfonamide, 259
6-[3-cyano-5-fluoro-1-(pyridin-4-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 260
2-(3-cyano-6-methyl-1-phenyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-
yl)pyrimidine-5-sulfonamide, 261
6-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 262
6-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 263
6-(3-cyano-1,6-dicyclobutyl-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 264
2-(3-cyano-1,6-dicyclobutyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-
yl)pyrimidine-5-sulfonamide, 265
2-(3-cyano-1,6-dicyclobutyl-1H-indol-2-yl)-N-(propan-2-yl)pyrimidine-
5-sulfonamide, 266
6-(3-cyano-1,6-dicyclobutyl-1H-indol-2-yl)-N-(propan-2-yl)pyridine-3-
sulfonamide, 267
6-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 268
N-{5-[3-cyano-1-cyclobutyl-6-(pyrimidin-2-yloxy)-1H-indol-2-yl]pyridin-
- 2-yl}-2-methylpropane-2-sulfonamide, 269
N-{5-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-1H-indol-2-
yl]pyridin-2-yl}-2-methylpropane-2-sulfonamide, 270
N-{6-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-1H-indol-2-
yl]pyridin-3-yl}cyclopropanesulfonamide, 271
N-{6-[3-cyano-1-cyclobutyl-6-(pyrimidin-2-yloxy)-1H-indol-2-yl]pyridin-
- 3-yl}propane-1-sulfonamide, 272
N-(6-{3-cyano-6-[(3-cyanopyridin-2-yl)oxy]-1-cyclobutyl-1H-indol-2-
yl}pyridin-3-yl)propane-1-sulfonamide, 273
N-(6-{3-cyano-6-[(3-cyanopyrazin-2-yl)oxy]-1-cyclobutyl-1H-indol-2-
yl}pyridin-3-yl)propane-1-sulfonamide, 274
N-{6-[3-cyano-1-cyclobutyl-6-(propan-2-yloxy)-1H-indol-2-yl]pyridazin--
3-yl}cyclopropanesulfonamide, 275
N-{6-[3-cyano-1-cyclobutyl-6-(propan-2-yloxy)-1H-indol-2-yl]pyridazin--
3-yl}methanesulfonamide, 276
N-{6-[3-cyano-1-cyclobutyl-6-(propan-2-yloxy)-1H-indol-2-yl]pyridazin--
3-yl}ethanesulfonamide, 277
N-[6-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)pyridazin-3-
yl]ethanesulfonamide, 278
N-[6-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)pyridazin-3-yl]-2-
methylpropane-2-sulfonamide, 279
N-{6-[3-cyano-1-(cyclopropylmethyl)-6-(propan-2-yloxy)-1H-indol-2-
yl]pyridin-3-yl}ethanesulfonamide, 280
N-{6-[3-cyano-1-(cyclopropylmethyl)-6-(propan-2-yloxy)-1H-indol-2-
yl]pyridin-3-yl}cyclopropanesulfonamide, 281
N-{6-[3-cyano-1-(cyclopropylmethyl)-6-(propan-2-yloxy)-1H-indol-2-
yl]pyridin-3-yl}propane-2-sulfonamide, 282
N-{6-[3-cyano-1-ethyl-6-(propan-2-yloxy)-1H-indol-2-yl]pyridin-3-yl}-N-
- (propan-2-yl)ethanesulfonamide, 283
N-{6-[3-cyano-1-(cyclopropylmethyl)-6-(2,2,2-trifluoroethoxy)-1H-indol-
- 2-yl]pyridin-3-yl}propane-2-sulfonamide, 284
N-{6-[3-cyano-1-(cyclopropylmethyl)-6-(2,2,2-trifluoroethoxy)-1H-indol-
- 2-yl]pyridin-3-yl}ethanesulfonamide, 285
N-{6-[3-cyano-1-ethyl-6-(propan-2-yloxy)-1H-indol-2-yl]pyridin-3-
yl}cyclopropanesulfonamide, 286
N-{6-[3-cyano-1-ethyl-6-(propan-2-yloxy)-1H-indol-2-yl]pyridin-3-
yl}propane-2-sulfonamide, 287
N-[5-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)pyridin-2-
yl]methanesulfonamide, 288
N-[5-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)pyridin-2-
yl]ethanesulfonamide, 289
N-[5-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)pyridin-2-
yl]propane-2-sulfonamide, 290
N-{5-[3-cyano-1-(cyclopropylmethyl)-6-(2,2,2-trifluoroethoxy)-1H-
indol-2-yl]pyridin-2-yl}ethanesulfonamide, 291
N-{5-[3-cyano-1-(cyclopropylmethyl)-6-(2,2,2-trifluoroethoxy)-1H-
indol-2-yl]pyridin-2-yl}propane-2-sulfonamide, 292
N-{5-[3-cyano-1-ethyl-6-(propan-2-yloxy)-1H-indol-2-yl]pyridin-2-yl}-N-
- (2,2-difluoroethyl)cyclopropanesulfonamide, 293
N-{5-[3-cyano-1-ethyl-6-(propan-2-yloxy)-1H-indol-2-yl]pyridin-2-yl}-N-
- (2-hydroxyethyl)cyclopropanesulfonamide, 294
N-{5-[3-cyano-1-ethyl-6-(propan-2-yloxy)-1H-indol-2-yl]pyridin-2-yl}-N-
- (cyanomethyl)cyclopropanesulfonamide, 295
N-{5-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]pyridin-
2-yl}-2-methylpropane-2-sulfonamide, 296
N-[6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)pyridin-3-
yl]cyclopropanesulfonamide, 297
N-[6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)pyridin-3-
yl]cyclopropanesulfonamide, 298
N-[6-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)pyridin-3-
yl]cyclopropanesulfonamide, 299
N-{5-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-
yl]pyridin-2-yl}-2-methylpropane-2-sulfonamide, 300
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 301
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1-
cyanoethyl)pyridine-3-sulfonamide, 302
2-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 303
2-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 304
6-[3-cyano-1-cyclohexyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 305
6-[3-cyano-1-cyclohexyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(1S)-1--
cyclopropylethyl]pyridine-3-sulfonamide, 306
2-[3-cyano-1-cyclohexyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 307
6-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 308
6-[3-cyano-1-(propan-2-yl)-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(1S)-
- 1-cyclopropylethyl]pyridine-3-sulfonamide, 309
6-[3-cyano-1-(cyclopropylmethyl)-6-(trifluoromethoxy)-1H-indol-2-yl]-
N-[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide, 310
6-(3-cyano-1-cyclopentyl-6-ethyl-1H-indol-2-yl)-N-(1,3-difluoropropan--
2-yl)pyridine-3-sulfonamide, 311
6-(3-cyano-1-cyclopentyl-6-ethyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 312
6-(3-cyano-1-cyclopentyl-6-ethyl-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 313
6-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 314
2-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 315
2-[3-cyano-1-cyclobutyl-6-(fluoromethyl)-1H-indol-2-yl]-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 316
6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 317
6-[3-cyano-1-cyclobutyl-6-(fluoromethyl)-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 318
6-[3-cyano-1-cyclobutyl-6-(fluoromethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 319
6-[3-cyano-1-cyclobutyl-6-(fluoromethyl)-1H-indol-2-yl]-N-[(2R)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide, 320
6-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(1S)-1-
- cyclopropylethyl]pyridine-3-sulfonamide, 321
2-[3-cyano-1-cyclobutyl-6-(morpholin-4-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 322
6-[3-cyano-1-cyclobutyl-6-(morpholin-4-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 323
2-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 324
2-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 325
2-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 326
2-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 327
6-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 328
6-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 329
6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 330
2-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 331
6-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 332
2-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]-N-(propan-2--
yl)pyrimidine-5-sulfonamide, 333
6-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]-N-(propan-2--
yl)pyridine-3-sulfonamide, 334
6-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 335
6-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 336
6-[3-cyano-5-fluoro-1-(4-methoxyphenyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 337
2-[3-cyano-5-fluoro-1-(4-methoxyphenyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 338
6-(3-cyano-1-cyclobutyl-6-ethyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 339
6-(3-cyano-1-cyclobutyl-5-ethyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 340
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 341
6-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 342
6-(3-cyano-1,6-dicyclobutyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-
yl)pyridine-3-sulfonamide, 343
6-(3-cyano-6-cyclobutyl-1-cyclopentyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 344
2-[3-cyano-6-cyclopropyl-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 345
6-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 346
6-(3,5-dicyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 347
6-[3,6-dicyano-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 348
6-[3,6-dicyano-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-(propan-2-
yl)pyridine-3-sulfonamide, 349
6-[3,6-dicyano-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 350
N-[(1S)-1-cyclopropylethyl]-6-[3,6-dicyano-1-(cyclopropylmethyl)-1H-
indol-2-yl]pyridine-3-sulfonamide, 351
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 352
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 353
6-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 354
6-(3-cyano-1-cyclohexyl-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 355
6-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 356
6-[3-cyano-5-fluoro-1-(4-methylphenyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 357
2-[3-cyano-5-fluoro-1-(4-methylphenyl)-1H-indol-2-yl]-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 358
6-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 359
6-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 360
6-(6-chloro-3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-
- trifluoropropan-2-yl]pyridine-3-sulfonamide, 361
2-[3-cyano-1-cyclobutyl-6-(fluoromethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 362
6-[3-cyano-1-cyclobutyl-6-(fluoromethyl)-1H-indol-2-yl]-N-[(2S)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide, 363
6-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 364
6-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 365
6-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 367
N-[(1S)-1-cyclopropylethyl]-2-(3,5-dicyano-1-cyclopentyl-1H-indol-2-
yl)pyrimidine-5-sulfonamide, 368
6-[3-cyano-6-(difluoromethoxy)-1-(4-fluorophenyl)-1H-indol-2-yl]-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 369
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 370
6-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 371
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-(1,1,1-trifluoro-2--
methylpropan-2-yl)pyridine-3-sulfonamide, 372
6-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 373
6-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 374
6-(3-cyano-1-cyclopentyl-5-ethyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 375
6-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 376
6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 377
2-[3-cyano-1-cyclobutyl-5-(fluoromethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 378
6-[3-cyano-1-cyclobutyl-5-(difluoromethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 379
2-[3-cyano-1-cyclobutyl-5-(difluoromethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 380
2-[3-cyano-1-cyclobutyl-5-(difluoromethyl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 381
6-(3-cyano-1-cyclopentyl-5-ethyl-1H-indol-2-yl)-N-(1,3-difluoropropan--
2-yl)pyridine-3-sulfonamide, 382
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,1,1-
trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 383
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 384
6-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 385
2-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 386
6-[3-cyano-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 387
6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 388
2-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2-yl]-N-(propan-
2-yl)pyrimidine-5-sulfonamide, 389
2-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 390
2-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 391
2-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 392
2-(3,5-dicyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 393
2-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 394
6-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 395
6-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 396
6-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 397
6-[3-cyano-1-(cyclopropylmethyl)-6-fluoro-1H-indol-2-yl]-N-[(2S)-1,1,1-
- trifluoropropan-2-yl]pyridine-3-sulfonamide, 398
2-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-1H-indol-2-yl]-
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 399
2-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 400
2-[3-cyano-6-(difluoromethoxy)-1-propyl-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 401
2-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 402
2-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 403
2-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 404
2-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 405
2-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 406
2-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 407
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 408
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 409
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 410
6-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 411
2-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 412
6-[3-cyano-1-(cyclohex-2-en-1-yl)-5-fluoro-1H-indol-2-yl]-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 413
6-[3-cyano-1-(cyclohex-2-en-1-yl)-5-fluoro-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 414
2-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 415
2-[6-chloro-3-cyano-1-(cyclopropylmethyl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 416
2-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 417
2-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 418
2-[6-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 419
2-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 420
2-[5-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 421
6-(3-cyano-1-cyclobutyl-7-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 422
6-(3-cyano-1-cyclobutyl-7-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 423
6-(3-cyano-1-cyclopentyl-7-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 424
6-(3-cyano-1-cyclopentyl-7-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 425
6-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 426
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 427
6-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 428
6-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 429
6-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 430
6-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 431
6-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 432
6-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 433
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 434
6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 435
6-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 436
6-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]-N-[(2S)-1,1,1-
- trifluoropropan-2-yl]pyridine-3-sulfonamide, 437
6-[6-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 438
6-[6-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 439
6-[3-cyano-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(propan-2-
yl)pyridine-3-sulfonamide, 440
6-(3-cyano-6-methyl-1-phenyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 441
6-(5-chloro-3-cyano-1-phenyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 442
6-[5-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 443
6-[5-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 444
6-(5-chloro-3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 445
6-(5-chloro-3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 446
6-(5-chloro-3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 447
2-(5-chloro-3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 448
2-(5-chloro-3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 449
2-[6-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 450
2-[6-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 451
2-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 452
2-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan--
2-yl)pyrimidine-5-sulfonamide, 453
6-(3-cyano-1-cyclobutyl-5-methoxy-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 454
2-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 455
2-[3-cyano-1-cyclobutyl-6-(propan-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 456
6-[3-cyano-1,6-di(propan-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan-2--
yl)pyridine-3-sulfonamide, 457
6-[3-cyano-1-cyclopentyl-6-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 458
6-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2-yl]-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 459
6-[3-cyano-1-cyclohexyl-6-(trifluoromethoxy)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 460
6-[3-cyano-1-(cyclopropylmethyl)-6-(propan-2-yl)-1H-indol-2-yl]-N-
(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide, 461
6-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 462
6-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 463
2-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 464
2-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 465
6-(3,6-dicyano-1-cyclobutyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-
yl)pyridine-3-sulfonamide, 466
2-(3,6-dicyano-1-cyclobutyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-
yl)pyrimidine-5-sulfonamide, 467
6-(3,6-dicyano-1-cyclobutyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 468
6-(3,6-dicyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-
yl)pyridine-3-sulfonamide, 469
2-(3,6-dicyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-
yl)pyrimidine-5-sulfonamide, 470
6-(3,6-dicyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 471
2-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 472
2-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 473
2-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(propan-
2-yl)pyrimidine-5-sulfonamide, 474
2-[3-cyano-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 475
2-[3-cyano-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 476
6-[3-cyano-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 477
2-[3-cyano-6-(difluoromethoxy)-1-(4-fluorophenyl)-1H-indol-2-yl]-N-
(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide, 478
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(1,1,1-trifluoro-2-
methylpropan-2-yl)pyridine-3-sulfonamide, 479
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,1,1-
trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 480
6-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-(1,1,1-trifluoro-2-
methylpropan-2-yl)pyridine-3-sulfonamide, 481
6-(3-cyano-1-cyclobutyl-6-ethyl-1H-indol-2-yl)-N-(1,1,1-trifluoro-2-
methylpropan-2-yl)pyridine-3-sulfonamide, 482
6-(3-cyano-1-cyclopentyl-6-fluoro-5-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 483
6-(3-cyano-1-cyclopentyl-6-fluoro-5-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 484
6-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 485
6-[3-cyano-5-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 486
6-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 487
6-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 488
6-[6-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 489
6-[6-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 490
6-[5-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 491
6-[5-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 492
6-(3-cyano-1-cyclobutyl-6-fluoro-5-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 493
6-(3-cyano-1-cyclobutyl-6-fluoro-5-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 494
2-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 495
2-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 496
2-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 497
2-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 498
2-[3-cyano-1-(cyclopropylmethyl)-6-fluoro-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 499
2-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 500
6-(3-cyano-1-cyclobutyl-5-methoxy-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 501
6-[3-cyano-6-cyclopropyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 502
6-[3-cyano-6-cyclopropyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
- trifluoropropan-2-yl]pyridine-3-sulfonamide, 503
6-[3-cyano-5-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 504
6-[3-cyano-5-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 505
6-(6-chloro-3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 506
6-(6-chloro-3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 507
2-(6-chloro-3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 508
6-(3-cyano-1-cyclopentyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 509
6-(3-cyano-1-cyclopentyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 510
6-(6-chloro-3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 511
6-(1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(1,3-difluoropropan-2-
yl)pyridine-3-sulfonamide, 512
6-[3-cyano-6-(difluoromethoxy)-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 513
6-(3-cyano-1-cyclohexyl-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 514
6-(6-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 515
6-(6-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 516
2-(6-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 517
2-(6-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 518
6-(3-cyano-1-cyclohexyl-6-methoxy-1H-indol-2-yl)-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 519
6-(3-cyano-1-cyclohexyl-6-methoxy-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 520
2-(3-cyano-1-cyclohexyl-6-methoxy-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 521
6-(6-chloro-3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 522
6-(6-chloro-3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 523
2-(6-chloro-3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-(propan-
2-yl)pyrimidine-5-sulfonamide, 524
2-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 525
6-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 526
2-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 527
2-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-(1,3-difluoropropan--
2-yl)pyrimidine-5-sulfonamide, 528
2-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 529
2-[3-cyano-5-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 530
2-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 531
2-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 532
6-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 533
6-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 534
6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2R)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 535
6-[3-cyano-1-cyclopentyl-5-(difluoromethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 536
2-[3-cyano-1-cyclopentyl-5-(difluoromethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 537
6-[3-cyano-1-cyclopentyl-5-(difluoromethyl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 538
6-[3-cyano-1-cyclopentyl-5-(difluoromethyl)-1H-indol-2-yl]-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 539
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,1,1-
trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 540
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 541
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 542
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N--
(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide, 543
N-tert-butyl-6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-
yl]pyridine-3-sulfonamide, 544
2-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 545
2-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 546
2-[3-cyano-5-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 547
2-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 548
2-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]-N-[(2S)-1,1,1-
- trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 549
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 550
6-(3-cyano-1-cyclobutyl-5-methoxy-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 551
2-(3-cyano-1-cyclobutyl-5-methoxy-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 552
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]pyridine-3-
sulfonamide, 553
6-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 554
6-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 555
6-(3-cyano-1-cyclobutyl-4,6-difluoro-5-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 556
6-(3-cyano-1-cyclobutyl-4,6-difluoro-5-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 557
2-(3-cyano-1-cyclobutyl-7-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 558
6-(3-cyano-1-cyclopentyl-4,6-difluoro-5-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 559
6-(3-cyano-1-cyclopentyl-4,6-difluoro-5-methyl-1H-indol-2-yl)-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 560
6-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 561
2-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 562
2-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 563
2-[3-cyano-5-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 564
6-[3-cyano-5-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 565
2-[3-cyano-5-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 566
2-[3-cyano-5-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 567
2-[3-cyano-5-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 568
1-cyclobutyl-6-(difluoromethoxy)-2-(5-sulfamoylpyridin-2-yl)-1H-
indole-3-carboxamide, 569
2-(3-cyano-1-cyclobutyl-5-methoxy-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 570
2-(3-cyano-1-cyclobutyl-5-methoxy-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyrimidine-5-sulfonamide, 571
6-(3-cyano-1-cyclopentyl-5-methoxy-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 572
2-(3-cyano-1-cyclopentyl-5-methoxy-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 573
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-
N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide, 574
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 575
6-(3-cyano-1-cyclopentyl-5-fluoro-6-hydroxy-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 576
6-(3-cyano-1-cyclopentyl-5-fluoro-6-hydroxy-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 577
6-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-(1,1,1--
trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 578
6-(3-cyano-1-cyclobutyl-7-fluoro-6-methyl-1H-indol-2-yl)-N-(1,1,1-
trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 579
6-(3-cyano-1-cyclopentyl-7-fluoro-6-methyl-1H-indol-2-yl)-N-(1,1,1-
trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 580
6-(3-cyano-1-cyclopentyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-
(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 581
1-cyclobutyl-6-(difluoromethoxy)-2-{5-[(1,3-difluoropropan-2-
yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide, 582
1-cyclobutyl-6-cyclopropyl-2-{5-[(1,3-difluoropropan-2-
yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide, 583
6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,1,-
1- trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 584
6-[3-cyano-6-cyclopropyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,1,1-
trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 585
6-(3-cyano-6-methyl-1-phenyl-1H-indol-2-yl)-N-(1,1,1-trifluoro-2-
methylpropan-2-yl)pyridine-3-sulfonamide, 586
2-(3-cyano-1-cyclopentyl-7-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 587
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclobutyl]pyridine-3-sulfonamide, 588
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[1-
(trifluoromethyl)cyclobutyl]pyridine-3-sulfonamide, 589
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 590
6-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[(1S)-1-
- cyclopropylethyl]pyridine-3-sulfonamide, 591
2-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 592
2-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[(1S)-1-
- cyclopropylethyl]pyrimidine-5-sulfonamide,
593
6-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 594
6-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[(1S)--
1- cyclopropylethyl]pyridine-3-sulfonamide, 595
6-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 596
6-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-(1,1,1-
- trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 597
2-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[(1S)--
1- cyclopropylethyl]pyrimidine-5-sulfonamide, 598
2-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-
(propan-2-yl)pyrimidine-5-sulfonamide, 599
2-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 600
2-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 601
6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 602
6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-(1,1,1-trifluo-
ro- 2-methylpropan-2-yl)pyridine-3-sulfonamide, 603
2-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-(propan-2-
yl)pyrimidine-5-sulfonamide, 604
6-[3-cyano-5-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 605
2-(3-cyano-1-cyclohexyl-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 606
6-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-[(1S)-1-
cyclopropylethyl]pyridine-3-sulfonamide, 607
6-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-(1,1,1-trifluoro-2--
methylpropan-2-yl)pyridine-3-sulfonamide, 608
6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 609
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 610
2-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 611
2-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 612
6-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]-N-(1,1,1-
trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 613
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 614
6-(3-cyano-1-cyclopentyl-4-fluoro-5-methyl-1H-indol-2-yl)-N-(1,1,1-
trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 615
6-(3-cyano-1-cyclopentyl-4-fluoro-5-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 616
6-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)-1H-indol-2-yl]--
N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide, 617
6-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)-1H-indol-2-yl]--
N-[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide, 618
6-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 619
2-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)-1H-indol-2-yl]--
N-[(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide, 620
2-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)-1H-indol-2-yl]--
N-(propan-2-yl)pyrimidine-5-sulfonamide, 621
2-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)-1H-indol-2-yl]--
N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide, 622
2-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 623
6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 624
N-tert-butyl-6-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-
yl]pyridine-3-sulfonamide, 625
6-(3-cyano-1-cyclopentyl-4-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 626
6-(3-cyano-1-cyclopentyl-4-fluoro-6-methyl-1H-indol-2-yl)-N-(1,1,1-
trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 627
6-(3-cyano-1-cyclobutyl-4-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 628
6-(3-cyano-1-cyclopentyl-4-fluoro-6-methyl-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 629
6-(3-cyano-1-cyclobutyl-4-fluoro-6-methyl-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 630
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-5-fluoro-1H-indol-2-yl)-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 631
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-5-fluoro-1H-indol-2-yl)-N-[(2R)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 632
6-(3-cyano-1-cyclopentyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-[(2R)-1,1,1-
- trifluoropropan-2-yl]pyridine-3-sulfonamide, 633
6-(3-cyano-1-cyclopentyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-
- trifluoropropan-2-yl]pyridine-3-sulfonamide, 634
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 635
6-[3-cyano-6-(difluoromethoxy)-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-
(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide, 636
6-[5-chloro-3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 637
6-(3-cyano-1-cyclopentyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 638
2-(3-cyano-1-cyclopentyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 639
6-(3-cyano-1-cyclopentyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 640
6-(3-cyano-1-cyclobutyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide, 641
6-(3-cyano-1-cyclobutyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-[(2R)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide, 642
6-(3-cyano-1-cyclobutyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 643
N-tert-butyl-6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-
yl)pyridine-3-sulfonamide, 644
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 645
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1-
methylcyclopropyl)pyridine-3-sulfonamide, 646
6-[1-cyclobutyl-6-(difluoromethoxy)-5-methyl-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 647
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-ethyl-1H-indol-2-yl]-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 648
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N--
[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 649
6-[3-cyano-6-(difluoromethoxy)-1-(4-fluorophenyl)-1H-indol-2-yl]-N-
[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 650
6-[3-cyano-6-cyclopropyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 651
N-tert-butyl-6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-
yl)pyridine-3-sulfonamide, 652
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-
cyclopropylpyridine-3-sulfonamide, 653
6-(3-cyano-1-cyclopentyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-[(2R)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 654
6-(3-cyano-1-cyclopentyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 655
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(propan-2-
yl)pyridine-3-sulfonamide, 656
2-(3-cyano-1-cyclopentyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 657
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(pyridine-2-yl)-1H-indol-2-
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 658
6-[5-chloro-3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N--
(1-methylcyclopropyl)pyridine-3-sulfonamide, 659
2-[5-chloro-3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N--
(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide, 660
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-methyl-1H-indol-2-yl]-
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 661
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-5-fluoro-1H-indol-2-yl)-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 662
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-5-fluoro-1H-indol-2-yl)-N-
[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 663
6-[3-cyano-6-(difluoromethoxy)-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-
(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 664
6-[3-cyano-6-(difluoromethoxy)-1-(4-fluorophenyl)-1H-indol-2-yl]-N-[1--
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 665
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-methyl-1H-indol-2-yl]-
N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 666
6-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 667
6-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 668
2-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyrimidine-5-sulfonamide, 669
6-(3-cyano-1-cyclopentyl-5-methoxy-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 670
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl-
]- N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 671
6-[3-cyano-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 672
6-(3-cyano-1-cyclopentyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-(1,1,1-
trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 673
6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 674
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-hydroxy-1H-indol-2-yl]-
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 675
6-(5-bromo-3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 676
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N--
(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 677
6-[3-cyano-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 678
6-(3-cyano-1-cyclohexyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 679
2-(3-cyano-1-cyclohexyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide, 680
6-(3-cyano-1-cyclohexyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 681
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,1,1-
trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 682
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2--
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 683
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclopentyl-5-fluoro-6-methy-
l- 1H-indole-3-carboxamide, 684
6-(5-bromo-3-cyano-1-cyclobutyl-6-hydroxy-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 685
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-(methylsulfanyl)-1H-
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
686
6-[3-cyano-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,1,1-trifluoro-
-2- methylpropan-2-yl)pyridine-3-sulfonamide, 687
6-[3-cyano-6-(difluoromethoxy)-1-(4-fluorophenyl)-1H-indol-2-yl]-N-
(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 688
6-[3-cyano-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2R)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 689
6-[3-cyano-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-(1,1,1-trifluo-
ro- 2-methylpropan-2-yl)pyridine-3-sulfonamide, 690
6-[3-cyano-6-(difluoromethoxy)-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[1--
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 691
6-(3-cyano-1-cyclopentyl-5-hydroxy-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 692
6-(5-bromo-3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 693
6-(3-cyano-1-cyclopentyl-5-hydroxy-6-methyl-1H-indol-2-yl)-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 694
6-(3-cyano-1-cyclopentyl-5-methoxy-6-methyl-1H-indol-2-yl)-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 695
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2R)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 696
6-[3-cyano-1-cyclobutyl-5-(2,2-difluoroethyl)-1H-indol-2-yl]-N-(1-
methylcyclopropyl)pyridine-3-sulfonamide, 697
6-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-5-fluoro-1H-indol-2-yl]--
N- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 698
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 699
1-cyclopentyl-5-fluoro-6-methyl-2-(5-{[(2R)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 700
1-cyclopentyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 701
1-cyclopentyl-5-fluoro-6-methyl-2-{5-[(1,1,1-trifluoro-2-methylpropan--
2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide, 702
6-[3-cyano-1-cyclobutyl-5-(2,2-difluoroethyl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 703
1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
704
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 705
6-(3-cyano-1-cyclohexyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,1,1-
trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 706
1-cyclohexyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 707
1-cyclohexyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyrimidin-2-yl)-1H-indole-3-carboxamide, 708
6-[5-chloro-3-cyano-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 709
N-{[6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)pyridin-3-
- yl]sulfonyl}-N-[(2R)-1,1,1-trifluoropropan-2-yl]acetamide, 710
N-tert-butyl-6-(3-cyano-1-cyclohexyl-5-fluoro-6-methyl-1H-indol-2-
yl)pyridine-3-sulfonamide, 711
6-(3-cyano-1-cyclobutyl-5-fluoro-6-hydroxy-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 712
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N--
(difluoromethyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide, 713
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-
N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 714
1-cyclohexyl-5-fluoro-6-methyl-2-{5-[(1,1,1-trifluoro-2-methylpropan-2-
- yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide, 715
1-cyclohexyl-5-fluoro-6-methyl-2-(5-sulfamoylpyridin-2-yl)-1H-indole-
3-carboxamide, 716
1-cyclohexyl-5-fluoro-6-methyl-2-(5-{[(2R)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 717 methyl
1-cyclohexyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxylate, 718
1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-2-(5-{[(2R)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
719
N-tert-butyl-6-(3-cyano-1-cyclobutyl-5-fluoro-6-hydroxy-1H-indol-2-
yl)pyridine-3-sulfonamide, 720
N-tert-butyl-6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-
indol-2-yl]pyridine-3-sulfonamide, 721
N-tert-butyl-6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-
indol-2-yl]-N-(difluoromethyl)pyridine-3-sulfonamide, 722
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-
yl]pyridine-3-sulfonamide, 723
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclobutyl-6-(difluoromethox-
y)- 5-fluoro-1H-indole-3-carboxamide, 724
6-{3-cyano-5-fluoro-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-indol-2-yl}-
-N- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 725
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methoxy-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 726
6-(3-cyano-1-cyclobutyl-6-ethoxy-5-fluoro-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 727
6-[1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 728
6-(1-cyclobutyl-5-fluoro-6-hydroxy-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 729
1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-2-{5-[(1,1,1-trifluoro-2-
methylpropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide,
730 1-cyclopentyl-5-fluoro-6-methyl-2-(5-{[1-
(trifluoromethyl)cyclopropyl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide, 731
1-cyclobutyl-6-cyclopropyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan--
2- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 732
1-cyclobutyl-5-fluoro-6-methyl-2-(5-{[(2R)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 733
5-chloro-1-cyclobutyl-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyrimidin-2-yl)-1H-indole-3-carboxamide, 734
5-chloro-1-cyclobutyl-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 735
5-chloro-1-cyclobutyl-6-methyl-2-(5-{[(2R)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 736
6-chloro-1-cyclobutyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 737
1-cyclobutyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 738
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluorobutan-2-yl]pyridine-3-sulfonamide, 739
6-[3-cyano-5-fluoro-6-methyl-1-(3-methylpyridin-2-yl)-1H-indol-2-yl]-N-
- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 740
6-{3-cyano-5-fluoro-6-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-
indol-2-yl}-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
741 1-cyclohexyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxylic acid, 742
6-[3-cyano-5-fluoro-1-(5-fluoropyridin-2-yl)-6-methyl-1H-indol-2-yl]-N-
- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 743
6-[3-cyano-1-(5-cyanopyridin-2-yl)-5-fluoro-6-methyl-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 744
6-[3-cyano-5-fluoro-6-methyl-1-(5-nitropyridin-2-yl)-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 745
5-chloro-1-cyclobutyl-2-[5-(propan-2-ylsulfamoyl)pyrimidin-2-yl]-1H-
indole-3-carboxamide, 746
1-cyclohexyl-6-(difluoromethoxy)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyrimidin-2-yl)-1H-indole-3-carboxamide, 747
1-cyclohexyl-6-(difluoromethoxy)-2-[5-(propan-2-
ylsulfamoyl)pyrimidin-2-yl]-1H-indole-3-carboxamide, 748
5-fluoro-1-(pyridin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 749
6-[3-cyano-5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indol-2-
yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 750
6-[3-cyano-5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indol-2-
yl]-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide,
751
6-[3-cyano-5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indol-2-
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 752
N-tert-butyl-6-[3-cyano-5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-
- 1H-indol-2-yl]pyridine-3-sulfonamide, 753
2-[3-cyano-5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indol-2-
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide,
754 methyl
1-cyclopentyl-5-fluoro-6-methyl-2-{5-[(1,1,1-trifluoro-2-
methylpropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxylate,
755 methyl
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclopentyl-5-fluoro-- 6-
methyl-1H-indole-3-carboxylate, 756 methyl
1-cyclopentyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxylate,
757
6-(3-cyano-1-cyclobutyl-5-methoxy-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 758
1-cyclopentyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxylic acid, 760
6-(1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 761
1-cyclopentyl-5-fluoro-N,6-dimethyl-2-(5-{[(2S)-1,1,1-trifluoropropan--
2- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 762
1-cyclopentyl-N-ethyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
763
1-cyclopentyl-5-fluoro-6-methyl-N-(propan-2-yl)-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
764
N-tert-butyl-6-(3-cyano-1-cyclobutyl-6-ethyl-5-fluoro-1H-indol-2-
yl)pyridine-3-sulfonamide, 765
1-cyclopentyl-5-fluoro-6-methyl-2-{5-[(1,1,1-trifluoro-2-methylpropan--
2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxylic acid, 766
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclopentyl-5-fluoro-6-methy-
l- 1H-indole-3-carboxylic acid, 767
5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-2-(5-{[(2R)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
768
5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-2-{5-[(1,1,1-trifluoro--
2-
methylpropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide,
769
5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
770 methyl
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclobutyl-5-fluoro-6- -
methyl-1H-indole-3-carboxylate, 771 methyl
1-cyclobutyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropa- -
2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxylate, 772
6-[3-cyano-1-cyclobutyl-5-fluoro-6-(methylsulfanyl)-1H-indol-2-yl]-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 773
6-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-4-fluoro-1H-
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
774 methyl
1-cyclobutyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropa- n-
2-yl]sulfamoyl}pyrimidin-2-yl)-1H-indole-3-carboxylate, 775
1-cyclobutyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyrimidin-2-yl)-1H-indole-3-carboxylic acid, 776
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclobutyl-5-fluoro-6-methyl-
- 1H-indole-3-carboxylic acid, 777
6-[3-cyano-6-ethyl-5-fluoro-1-(5-fluoropyridin-2-yl)-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 778
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 780
6-chloro-1-cyclobutyl-2-[5-(propan-2-ylsulfamoyl)pyrimidin-2-yl]-1H-
indole-3-carboxamide, 781
1-cyclobutyl-2-[5-(propan-2-ylsulfamoyl)pyrimidin-2-yl]-6-
(trifluoromethoxy)-1H-indole-3-carboxamide, 782
1-cyclopentyl-2-[5-(propan-2-ylsulfamoyl)pyrimidin-2-yl]-6-
(trifluoromethoxy)-1H-indole-3-carboxamide, 783
1-cyclopentyl-5-fluoro-N,N,6-trimethyl-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
784
6-[3-cyano-6-(difluoromethoxy)-4-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-
- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 785
6-[5-chloro-3-cyano-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 786
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-propyl-1H-indol-2-yl]-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 787
6-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-5-fluoro-1H-
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
788
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-propyl-1H-indol-2-yl]-N-
[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 789
6-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-5-fluoro-1H-
indol-2-yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
790
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N--
(1,1,1-trifluorobutan-2-yl)pyridine-3-sulfonamide, 791
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N--
phenylpyridine-3-sulfonamide, 793
1-cyclobutyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxylic acid, 794
2-[5-(tert-butylsulfamoyl)pyrimidin-2-yl]-1-cyclobutyl-5-fluoro-6-meth-
yl- 1H-indole-3-carboxylic acid, 795
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclobutyl-5-fluoro-N,6-
dimethyl-1H-indole-3-carboxamide, 796
6-(3-cyano-1-cyclobutyl-5-hydroxy-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 797
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-4-fluoro-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 798
1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-2-[5-
(phenylsulfamoyl)pyridin-2-yl]-1H-indole-3-carboxamide, 799
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclopentyl-5-fluoro-N,6-
dimethyl-1H-indole-3-carboxamide, 800
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclobutyl-5-fluoro-6-methyl-
- 1H-indole-3-carboxamide, 801
1-cyclobutyl-5-fluoro-N,6-dimethyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 802
2-[5-(tert-butylsulfamoyl)pyrimidin-2-yl]-1-cyclobutyl-5-fluoro-N,6-
dimethyl-1H-indole-3-carboxamide, 803
6-[5-chloro-3-cyano-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 804
6-[5-chloro-3-cyano-1-(5-fluoropyridin-2-yl)-6-methyl-1H-indol-2-yl]-N-
- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 805
N-tert-butyl-6-(3-cyano-1-cyclobutyl-5-hydroxy-6-methyl-1H-indol-2-
yl)pyridine-3-sulfonamide, 806
1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
807
6-(3-cyano-1-cyclobutyl-5-hydroxy-6-methyl-1H-indol-2-yl)-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 808
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N--
[1-(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 809
1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-2-(5-{[1-
(trifluoromethyl)cyclopropyl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide, 810
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-4-methyl-1H-
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
811
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-7-methyl-1H-
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
812
6-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-5-fluoro-1H-
indol-2-yl]pyridine-3-sulfonamide, 813
6-(3-cyano-1-cyclobutyl-5-fluoro-6-hydroxy-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 814
6-[3-cyano-5-fluoro-1-(3-fluoropyridin-2-yl)-6-methyl-1H-indol-2-yl]-N-
- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 815
6-[3-cyano-5-fluoro-1-(6-fluoropyridin-2-yl)-6-methyl-1H-indol-2-yl]-N-
- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 816
6-[3-cyano-5-fluoro-1-(4-methoxypyridin-2-yl)-6-methyl-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 817
6-[3-cyano-5-fluoro-6-methyl-1-(pyrazin-2-yl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 818
6-[3-cyano-6-cyclopropyl-5-fluoro-1-(5-fluoropyridin-2-yl)-1H-indol-2--
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 819
6-[3-cyano-6-cyclopropyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 820
6-[3-cyano-6-cyclopropyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 821
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluorobutan-2-yl]pyridine-3-sulfonamide, 822
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-4--
methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
823 N-tert-butyl-6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-
yl]pyridine-3-sulfonamide, 824
N-tert-butyl-6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2-yl)-1H-indol--
2- yl]pyridine-3-sulfonamide, 825
1-cyclobutyl-6-(difluoromethoxy)-4-fluoro-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
826
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluorobutan-2-yl]pyridine-3-sulfonamide, 827
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-5--
methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
828
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclobutyl-5-hydroxy-6-methy-
l- 1H-indole-3-carboxamide, 829
1-cyclopentyl-6-cyclopropyl-5-fluoro-2-(5-{[(2R)-1,1,1-trifluoropropan-
- 2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 830
1-cyclopentyl-6-ethyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 831
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-5-fluoro-1H-indol-2-yl)-N-
(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 832
N-tert-butyl-6-(3-cyano-1-cyclopentyl-6-cyclopropyl-5-fluoro-1H-indol--
2-yl)pyridine-3-sulfonamide, 833
1-cyclobutyl-5-hydroxy-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 834
1-cyclopentyl-5-methoxy-6-methyl-2-(5-{[(2R)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 835
1-cyclohexyl-5-fluoro-6-methyl-2-(5-{[1-
(trifluoromethyl)cyclopropyl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxylic acid, 836
N-[6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)pyridin-3--
yl]-N'-[(2S)-1,1,1-trifluoropropan-2-yl]sulfuric diamide, 837
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-5-methyl-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 838
1-cyclopentyl-6-cyclopropyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan-
- 2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 839
6-(difluoromethoxy)-4-fluoro-1-(propan-2-yl)-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
840
1-(cyclopropylmethyl)-6-(difluoromethoxy)-4-fluoro-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
841
1-cyclopentyl-5-hydroxy-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 842
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-4-methyl-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 843
6-[3-cyano-5-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 844
6-[3-cyano-1-(3-fluoropyridin-2-yl)-5-methyl-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 845
6-[3-cyano-5-methyl-1-(pyrazin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 846
5-methyl-1-(pyrimidin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 847
6-[3-cyano-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-4-methyl-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 848
6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-4-methyl-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 849
6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan--
2- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 850
1-cyclopentyl-6-cyclopropyl-5-fluoro-2-{5-[(1,1,1-trifluoro-2-
methylpropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide,
851
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-4-methyl-
- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 852
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-4-methyl-N-
- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 853
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-4-
methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
854
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-4-methyl--
N-[(2S)- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 855
N-tert-butyl-6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-
- yl]pyridine-3-sulfonamide, 856
6-(3-cyano-1-cyclohexyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 857
1-cyclohexyl-5-fluoro-6-methyl-2-(5-{[1-
(trifluoromethyl)cyclopropyl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide, 858
6-(3-cyano-1-cyclobutyl-6-ethyl-4-methoxy-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 859
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-(1,1,1-
- trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 860
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-(1-
methylcyclopropyl)pyridine-3-sulfonamide, 861
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-(1-
methylcyclopropyl)-N-(pyrimidin-2-yl)pyridine-3-sulfonamide, 862
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-
N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 863
1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-2-{5-[(1,1,1-trifluoro-2-
methylpropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide,
864
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 865
6-[3-cyano-5-fluoro-6-methyl-1-(5-methylpyrazin-2-yl)-1H-indol-2-yl]-
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 866
6-[3-cyano-5-fluoro-1-(4-methoxypyrimidin-2-yl)-6-methyl-1H-indol-2-
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 867
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-5-methyl-
- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 868
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-2-methyl-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 869
N-tert-butyl-6-[6-ethyl-5-fluoro-3-(methylsulfonyl)-1-(pyrimidin-2-yl)-
- 1H-indol-2-yl]pyridine-3-sulfonamide, 870
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-5-methyl-N-
- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 871
1-cyclopentyl-6-ethyl-5-fluoro-2-{5-[(1,1,1-trifluoro-2-methylpropan-2-
- yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide, 872
1-cyclopentyl-6-ethyl-5-fluoro-2-(5-{[1-
(trifluoromethyl)cyclopropyl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide, 873
6-[3-cyano-5-fluoro-6-methyl-1-(4-methylpyrimidin-2-yl)-1H-indol-2-yl]-
- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 874
5-fluoro-6-methyl-1-(pyridin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 875
5-fluoro-6-methyl-1-(pyrazin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 876
5-fluoro-1-(5-fluoropyridin-2-yl)-6-methyl-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
877 5-fluoro-1-(6-fluoropyridin-2-yl)-6-methyl-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
878
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2R)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 879
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 880
6-[3-cyano-6-ethyl-5-fluoro-1-(5-fluoropyridin-2-yl)-1H-indol-2-yl]-N--
[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 881
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-2-methyl-
- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 882
N-tert-butyl-6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-
yl]pyridine-3-sulfonamide, 883
2-[5-(tert-butylsulfamoy)pyridin-2-yl]-6-ethyl-5-fluoro-1-(pyridin-2-y-
l)- 1H-indole-3-carboxamide, 884
N-tert-butyl-6-(3-cyano-6-ethyl-5-fluoro-1-phenyl-1H-indol-2-yl)pyridi-
ne- 3-sulfonamide, 885
6-[3-cyano-5-fluoro-6-methyl-1-(5-methylpyridin-2-yl)-1H-indol-2-yl]-N-
- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 886
6-[3-cyano-5-fluoro-6-methyl-1-(4-methylpyridin-2-yl)-1H-indol-2-yl]-N-
- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 887
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-2-methyl-N-
- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 888
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-5-
methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
889
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-5-methyl--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 890
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-4-methyl-
- N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 891
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-4-methyl-N-
- [(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 892
6-[3-cyano-5-fluoro-6-methyl-1-(pyridazin-3-yl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 893
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-3-yl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 894
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-5-yl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 895
6-[6-bromo-3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 896
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-4-yl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 897
6-[3-cyano-1-(pyrazin-2-yl)-5-(trifluoromethyl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 898
6-[3-cyano-1-(pyrazin-2-yl)-5-(trifluoromethoxy)-1H-indol-2-yl]-N-[(2S-
)- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 899
N-tert-butyl-6-[3-cyano-6-ethyl-5-fluoro-1-(pyrazin-2-yl)-1H-indol-2-
yl]pyridine-3-sulfonamide, 900
N-tert-butyl-6-[3-cyano-6-ethyl-5-fluoro-1-(3-fluoropyridin-2-yl)-1H-i-
ndol-2- yl]pyridine-3-sulfonamide, 901
6-[3-cyano-6-fluoro-5-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 902
5-fluoro-1-(3-fluoropyridin-2-yl)-6-methyl-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
903
6-[5-fluoro-6-methyl-1-(1,3-thiazol-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
- trifluoropropan-2-yl]pyridine-3-sulfonamide, 904
5-fluoro-6-methyl-1-(5-methylpyrazin-2-yl)-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
905 5-fluoro-6-methyl-1-(4-methylpyrimidin-2-yl)-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
906
5-fluoro-1-(4-methoxypyrimidin-2-yl)-6-methyl-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
907
6-[6-acetyl-3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 908
6-[3-cyano-6-ethenyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S-
)- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 909
6-ethyl-5-fluoro-1-(pyridin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2--
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 910
6-(3-cyano-1-cyclopropyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1-
- trifluoropropan-2-yl]pyridine-3-sulfonamide, 911
6-[3-cyano-5-fluoro-6-(1-hydroxyethyl)-1-(pyrimidin-2-yl)-1H-indol-2-
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 912
5-fluoro-6-methyl-1-(pyridazin-3-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-
-2- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 913
5-fluoro-6-methyl-1-(pyridin-3-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 914
6-[1-(5-chloropyrimidin-2-yl)-3-cyano-5-fluoro-6-methyl-1H-indol-2-yl]-
- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 915
6-[3-cyano-5-fluoro-6-methyl-1-(6-methylpyrazin-2-yl)-1H-indol-2-yl]-
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 916
5-methyl-1-(pyrazin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 917
6-[3-cyano-6-fluoro-5-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 918
6-fluoro-5-methyl-1-(pyrimidin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-
-2- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 919
6-[3-cyano-6-fluoro-5-methyl-1-(pyrazin-2-yl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 920
6-[3-cyano-1-(4-fluorophenyl)-5-methyl-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 921
6-(3-cyano-5-methyl-1-phenyl-1H-indol-2-yl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 922
6-[3-cyano-1-(pyrimidin-2-yl)-5-(trifluoromethyl)-1H-indol-2-yl]-N-[(2-
S)- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 923
6-[3-cyano-5-fluoro-6-methyl-1-(6-methylpyridin-2-yl)-1H-indol-2-yl]-N-
- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 924
6-[3-cyano-5-fluoro-1-(5-fluoropyrimidin-2-yl)-6-methyl-1H-indol-2-yl]-
- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 925
6-[3-cyano-5-fluoro-6-methyl-1-(5-methylpyrimidin-2-yl)-1H-indol-2-yl]-
- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 926
6-[3-cyano-5-fluoro-1-(4-fluoropyridin-2-yl)-6-methyl-1H-indol-2-yl]-N-
- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 927
6-[3-cyano-5-fluoro-6-(2-methyl-1,3-dioxolan-2-yl)-1-(pyrimidin-2-yl)--
1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,-
928
1-cyclohexyl-6-(difluoromethoxy)-5-fluoro-2-{5-[(1,1,1-trifluoro-2-
methylpropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxylic
acid, 929
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrazin-2-yl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 930
6-[3-cyano-6-ethyl-5-fluoro-1-(6-fluoropyridin-2-yl)-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 931
6-[3-cyano-6-ethyl-5-fluoro-1-(5-methylpyridin-2-yl)-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 932
6-[3-cyano-6-ethyl-5-fluoro-1-(4-methylpyridin-2-yl)-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 933
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-4-yl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 934
6-[3-cyano-5-fluoro-6-methyl-1-(1,3-thiazol-2-yl)-1H-indol-2-yl]-N-[(2-
S)- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 935
6-[3-cyano-6-ethyl-5-fluoro-1-(1,3-thiazol-2-yl)-1H-indol-2-yl]-N-[(2S-
)- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 936
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-
- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 937
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(2-methylpropyl)-1H-indol-
2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
938
6-[6-bromo-3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-tert-
butylpyridine-3-sulfonamide, 939
N-tert-butyl-6-[3,6-diacetyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-
yl]pyridine-3-sulfonamide, 940
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(2-hydroxyethyl)-1H-indol-
2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
941
6-[3-cyano-1-(1,6-dihydropyrimidin-2-yl)-6-ethyl-5-fluoro-1H-indol-2-
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 942
6-[1-(5-chloropyrimidin-2-yl)-3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl]--
N- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 943
6-[3-cyano-6-ethyl-5-fluoro-1-(2-methylpyrimidin-4-yl)-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 944
6-[5-fluoro-1-(2-fluoropyridin-4-yl)-6-methyl-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 945
6-[3-cyano-5-fluoro-1-(5-fluoropyridin-3-yl)-6-methyl-1H-indol-2-yl]-N-
- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 946
6-[3-cyano-6-ethyl-5-fluoro-1-(5-fluoropyrimidin-2-yl)-1H-indol-2-yl]--
N- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 947
6-[3-chloro-6-cyclopropyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-
- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 948
6-[3-cyano-1-(5-fluoropyrimidin-2-yl)-5-methyl-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 949
6-[3-cyano-6-fluoro-1-(5-fluoropyrimidin-2-yl)-5-methyl-1H-indol-2-yl]-
- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 950
6-[3-cyano-1-(pyrimidin-2-yl)-6-(trifluoromethyl)-1H-indol-2-yl]-N-[(2-
S)- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 951
6-[3-cyano-1-(pyrazin-2-yl)-6-(trifluoromethyl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 952
6-[3-cyano-1-(pyridin-2-yl)-6-(trifluoromethyl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 953
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-
(cyclobutylmethyl)pyridine-3-sulfonamide, 954
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-3-yl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 955
6-[3-cyano-6-ethyl-5-fluoro-1-(4-methoxypyridin-2-yl)-1H-indol-2-yl]-N-
- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 956
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoro(2-deuterium)propan-2-yl]pyridine-3-sulfonamide, 957
6-[5-fluoro-6-methyl-1-(1,3-thiazol-4-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
- trifluoropropan-2-yl]pyridine-3-sulfonamide, 958
6-[5-fluoro-6-methyl-1-(1,3,4-thiadiazol-2-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 959
6-[5-fluoro-6-methyl-1-(1,3-thiazol-5-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
- trifluoropropan-2-yl]pyridine-3-sulfonamide, 960
6-[3-cyano-5-fluoro-6-methyl-1-(1,3-thiazol-4-yl)-1H-indol-2-yl]-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 961
6-[3-cyano-5-fluoro-1-(5-fluoro-6-methylpyridin-2-yl)-6-methyl-1H-indo-
l- 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
962
6-[1-(6-chloropyridin-2-yl)-3-cyano-5-fluoro-6-methyl-1H-indol-2-yl]-N-
- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 963
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-5-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 964
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-4-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 965
6-[1-(3-chloropyridin-2-yl)-3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 966
6-[1-(5-chloropyridin-2-yl)-3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 967
6-[3-cyano-5-fluoro-6-(prop-2-en-1-yl)-1-(pyrimidin-2-yl)-1H-indol-2-y-
l]- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 968
6-[3-chloro-5-fluoro-6-(prop-2-en-1-yl)-1-(pyrimidin-2-yl)-1H-indol-2--
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 969
6-[5-fluoro-6-(prop-2-en-1-yl)-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2-
S)- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 970
6-[3-cyano-5-fluoro-6-(2-hydroxyethyl)-1-(pyrimidin-2-yl)-1H-indol-2-
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 971
6-[1-(3-chloropyridin-2-yl)-3-cyano-5-fluoro-6-methyl-1H-indol-2-yl]-N-
- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 972
6-[3-chloro-5-fluoro-6-methyl-1-(1,3,4-thiadiazol-2-yl)-1H-indol-2-yl]-
-N- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 973
6-[3-cyano-5-fluoro-6-methyl-1-(1,3-thiazol-5-yl)-1H-indol-2-yl]-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 974
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-4-yl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 975
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridazin-3-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 976
6-[3-cyano-6-ethyl-5-fluoro-1-(5-methylpyrimidin-2-yl)-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 977
6-[3-cyano-5-fluoro-6-methyl-1-(1,3,4-thiadiazol-2-yl)-1H-indol-2-yl]--
N-[(2S)- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 978
6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-2-{5-[(1,1,1-trifluoro-2-
methylpropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide,
979 6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-2-(5-{[1-
(trifluoromethyl)cyclopropyl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide, 980
6-ethyl-5-fluoro-1-(4-methylpyridin-2-yl)-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
981 6-ethyl-5-fluoro-1-(5-fluoropyridin-2-yl)-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
982 6-ethyl-5-fluoro-1-(2-methylpyrimidin-4-yl)-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
983
6-[1-(5-chloropyridin-3-yl)-3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 984
6-{3-cyano-5-fluoro-1-[5-(hydroxymethyl)-1,3-thiazol-2-yl]-6-methyl-
1H-indol-2-yl}-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,-
985 methyl
2-[3-cyano-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan--
2-yl]sulfamoyl}pyridin-2-yl)-1H-indol-1-yl]-1,3-thiazole-5-carboxylate,
986 methyl
2-[3-cyano-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-trifluoropropan--
2-yl]sulfamoyl}pyridin-2-yl)-1H-indol-1-yl]-1,3-thiazole-4-carboxylate,
987
6-[5-fluoro-6-methyl-1-(thiophen-3-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 988
6-[5-fluoro-1-(furan-3-yl)-6-methyl-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 989
6-[5-fluoro-6-methyl-1-(thiophen-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 990
6-[3-cyano-5-fluoro-6-methyl-1-(thiophen-2-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 991
6-[3-cyano-5-fluoro-1-(furan-3-yl)-6-methyl-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 992
6-[3-cyano-5-fluoro-6-methyl-1-(thiophen-3-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 993
6-[1-(4-chloropyridin-2-yl)-3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 994
6-ethyl-5-fluoro-1-(pyrazin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2--
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide 995
6-ethyl-5-fluoro-1-(6-fluoropyridin-2-yl)-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
996 5-chloro-1-cyclobutyl-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 997
1-cyclobutyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 998
2-{5-[(tert-butylsulfonyl)amino]pyridin-2-yl}-1-cyclohexyl-6-ethyl-5-f-
luoro- 1H-indole-3-carboxylic, 999
2-{5-[(tert-butylsulfonyl)amino]pyridin-2-yl}-1-cyclohexyl-6-ethyl-5-f-
luoro- 1H-indole-3-carboxamide, 1000
6-[3-cyano-5-fluoro-6-methyl-1-(3-methylthiophen-2-yl)-1H-indol-2-yl]-
- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1001
6-[3-cyano-1-(4,6-difluoropyridin-2-yl)-5-fluoro-6-methyl-1H-indol-2--
yl]- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
1002
6-[3-cyano-6-ethyl-5-fluoro-1-(4-fluorophenyl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1003
6-[1-(4-chlorophenyl)-3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
1004
6-[3-cyano-6-ethyl-5-fluoro-1-(4-methylphenyl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1005
6-[3-cyano-6-ethyl-5-fluoro-1-(4-methoxyphenyl)-1H-indol-2-yl]-N-[(2S-
)- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1006
6-{3-cyano-6-ethyl-5-fluoro-1-[4-(trifluoromethyl)phenyl]-1H-indol-2--
yl}-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1007
6-[3-cyano-1-(4-cyanophenyl)-6-ethyl-5-fluoro-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1008
6-[3-cyano-6-ethyl-5-fluoro-1-(3-fluorophenyl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1009
6-[3-cyano-6-ethyl-5-fluoro-1-(3-methylphenyl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1010
6-[3-cyano-6-ethyl-5-fluoro-1-(3-methoxyphenyl)-1H-indol-2-yl]-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1011
6-{3-cyano-6-ethyl-5-fluoro-1-[3-(trifluoromethyl)phenyl]-1H-indol-2--
yl}-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1012
6-[3-cyano-1-(3-cyanophenyl)-6-ethyl-5-fluoro-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1013
6-[3-cyano-5-fluoro-1-(2-fluoropyridin-4-yl)-6-methyl-1H-indol-2-yl]--
N- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1014
6-[3-cyano-5-fluoro-1-(3-fluoropyridin-4-yl)-6-methyl-1H-indol-2-yl]--
N- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1015
6-[3-cyano-5-fluoro-1-(6-fluoropyridin-3-yl)-6-methyl-1H-indol-2-yl]--
N- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1016
6-[3-cyano-5-fluoro-6-methyl-1-(1-methyl-1H-pyrazol-4-yl)-1H-indol-2--
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1017
6-[3-cyano-5-fluoro-6-methyl-1-(5-methyl-1,3-thiazol-2-yl)-1H-indol-2-
- yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
1018
6-[1-(3-chlorophenyl)-3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1019
6-ethyl-5-fluoro-1-(4-fluorophenyl)-2-(5-{[(2S)-1,1,1-trifluoropropan-
-2- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 1020
1-(4-chlorophenyl)-6-ethyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan-
-2- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 1021
6-ethyl-5-fluoro-1-(4-methylphenyl)-2-(5-{[(2S)-1,1,1-trifluoropropan-
-2- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 1022
6-ethyl-5-fluoro-1-[4-(trifluoromethyl)phenyl]-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1023
6-ethyl-5-fluoro-1-(3-fluorophenyl)-2-(5-{[(2S)-1,1,1-trifluoropropan-
-2- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 1024
6-ethyl-5-fluoro-1-(3-methylphenyl)-2-(5-{[(2S)-1,1,1-trifluoropropan-
-2- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 1025
6-ethyl-5-fluoro-1-(3-methoxyphenyl)-2-(5-{[(2S)-1,1,1-trifluoropropa-
n- 2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 1026
6-ethyl-5-fluoro-1-[3-(trifluoromethyl)phenyl]-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1027
1-(3-chlorophenyl)-6-ethyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan-
-2- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 1028
2-{5-[(tert-butylsulfonyl)amino]pyrimidin-2-yl}-1-cyclohexyl-6-ethyl--
5- fluoro-1H-indole-3-carboxylic acid, 1029
2-{2-[(tert-butylsulfonyl)amino]pyrimidin-5-yl}-1-cyclohexyl-6-ethyl--
5- fluoro-1H-indole-3-carboxylic acid, 1030
6-[3-cyano-5-fluoro-6-methyl-1-(3-methyl-1H-pyrazol-4-yl)-1H-indol-2--
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1031
6-[3-cyano-5-fluoro-6-methyl-1-(5-methylthiophen-2-yl)-1H-indol-2-yl]-
- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1032
6-[1-(5-chlorothiophen-2-yl)-3-cyano-5-fluoro-6-methyl-1H-indol-2-yl]-
- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1033
6-[3-cyano-1-(5-cyanothiophen-2-yl)-5-fluoro-6-methyl-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1034
6-[3-cyano-5-fluoro-6-methyl-1-(5-sulfamoylthiophen-2-yl)-1H-indol-2--
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1035
6-[1-(5-acetylthiophen-2-yl)-3-cyano-5-fluoro-6-methyl-1H-indol-2-yl]-
- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1036
2-{2-[(tert-butylsulfonyl)amino]pyrimidin-5-yl}-1-cyclohexyl-6-ethyl--
5- fluoro-1H-indole-3-carboxamide, 1037
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-cyclohexyl-6-ethyl-5--
fluoro- 1H-indole-3-carboxamide, 1038
6-[3-cyano-5-fluoro-6-methyl-1-(4-methyl-1,3-thiazol-2-yl)-1H-indol-2-
- yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
1039 6-ethyl-5-fluoro-1-(5-methylpyridin-2-yl)-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1040
6-ethyl-5-fluoro-1-(pyridin-3-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 1041
6-ethyl-5-fluoro-1-(pyrimidin-4-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-
-2- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 1042
1-(3-chloropyridin-2-yl)-6-ethyl-5-fluoro-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1043 1-(5-chloropyridin-2-yl)-6-ethyl-5-fluoro-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1044 1-(5-chloropyridin-3-yl)-6-ethyl-5-fluoro-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1045
6-ethyl-5-fluoro-1-(pyridin-4-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-2-
- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 1046
6-ethyl-5-fluoro-1-(pyridazin-3-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan-
-2- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 1047
6-ethyl-5-fluoro-1-(5-methylpyrimidin-2-yl)-2-(5-{[(2S)-1,1,1-trifluo-
ropropan- 2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1048 1-(4-chloropyridin-2-yl)-6-ethyl-5-fluoro-2-(5-{[(2S)-1,1,1-
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide,
1055
6-[1-(2-acetylthiophen-3-yl)-3-cyano-5-fluoro-6-methyl-1H-indol-2-yl]-
- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1056
6-[3-cyano-5-fluoro-6-methyl-1-(4-methylthiophen-3-yl)-1H-indol-2-yl]-
- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1057
6-[1-(2-chlorothiophen-3-yl)-3-cyano-5-fluoro-6-methyl-1H-indol-2-yl]-
- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1058
6-[3-cyano-5-fluoro-6-methyl-1-(5-methylthiophen-3-yl)-1H-indol-2-yl]-
- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1059
6-[5-fluoro-6-methyl-1-(1,3-oxazol-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
- trifluoropropan-2-yl]pyridine-3-sulfonamide, 1060
6-[1-(5-cyanofuran-2-yl)-5-fluoro-6-methyl-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1061
6-[3-cyano-1-(3,4-difluorophenyl)-6-ethyl-5-fluoro-1H-indol-2-yl]-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1062
6-[1-(3-chloro-4-fluorophenyl)-3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl-
]- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1063
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-cyclohexyl-6-
(difluoromethoxy)-5-fluoro-1H-indole-3-carboxamide, 1064
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-cyclohexyl-6-
(difluoromethoxy)-5-fluoro-1H-indole-3-carboxylic acid, 1065
N-{5-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-
yl]pyridin-2-yl}-2-methylpropane-2-sulfonamide, 1072
6-[3-cyano-1-(3-cyanofuran-2-yl)-5-fluoro-6-methyl-1H-indol-2-yl]-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1073
6-[3-cyano-5-fluoro-6-methyl-1-(1,3-oxazol-2-yl)-1H-indol-2-yl]-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1074
6-[3-cyano-1-(4-cyano-1,3-oxazol-2-yl)-5-fluoro-6-methyl-1H-indol-2-
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1075
6-[3-cyano-6-ethyl-5-fluoro-1-(2-fluorophenyl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1078
6-{3-cyano-6-[(1,1-dideuterium)ethyl]-5-fluoro-1-(pyrimidin-2-yl)-1H--
indol-2-yl}-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
1079
6-{3-cyano-6-[(1,1-dideuterium)ethyl]-5-fluoro-1-(pyrimidin-2-yl)-1H--
indol-2-yl}-N-[(2S)-1,1,1-trifluoro(2-deuterium)propan-2-yl]pyridine-3-
sulfonamide, 1080
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-[(1S)-1-cyclopropylet-
hyl]- 6-(difluoromethoxy)-5-fluoro-1H-indole-3-carboxylic acid,
1081
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-[(1S)-1-cyclopropylet-
hyl]- 6-(difluoromethoxy)-5-fluoro-1H-indole-3-carboxamide, 1082
N-(5-{3-cyano-1-[(1S)-1-cyclopropylethyl]-6-ethyl-5-fluoro-1H-indol-2-
- yl}pyridin-2-yl)-2-methylpropane-2-sulfonamide, 1083
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-[(1S)-1-cyclopropylet-
hyl]- 6-ethyl-5-fluoro-1H-indole-3-carboxamide, 1084
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-[(1R)-1-cyclopropylet-
hyl]- 6-(difluoromethoxy)-5-fluoro-1H-indole-3-carboxylic acid,
1085
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-[(1R)-1-cyclopropylet-
hyl]- 6-(difluoromethoxy)-5-fluoro-1H-indole-3-carboxamide, 1086
2-{6-[(tert-butylsulfonyl)amino]-4-methylpyridin-3-yl}-1-[(1R)-1-
cyclopropylethyl]-6-(difluoromethoxy)-5-fluoro-1H-indole-3-carboxylic
acid, 1087
2-{6-[(tert-butylsulfonyl)amino]-4-methylpyridin-3-yl}-1-[(1R)-1-
cyclopropylethyl]-6-(difluoromethoxy)-5-fluoro-1H-indole-3-
carboxamide, 1088
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-cyclohexyl-6-cyclopro-
pyl- 4-fluoro-1H-indole-3-carboxamide, 1092
N-[6-(3-cyano-1-cyclohexyl-6-cyclopropyl-4-fluoro-1H-indol-2-
yl)pyridin-3-yl]-2-methylpropane-2-sulfonamide, 1093
2-{6-[(tert-butylsulfonyl)amino]-2-methylpyridin-3-yl}-6-
(difluoromethoxy)-5-fluoro-1-(propan-2-yl)-1H-indole-3-carboxylic
acid, 1094
2-{6-[(tert-butylsulfonyl)amino]-2-methylpyridin-3-yl}-1-[(1R)-1-
cyclopropylethyl]-6-(difluoromethoxy)-5-fluoro-1H-indole-3-carboxylic
acid, 1095
2-{6-[(tert-butylsulfonyl)amino]-2-methylpyridin-3-yl}-6-
(difluoromethoxy)-5-fluoro-1-(propan-2-yl)-1H-indole-3-carboxamide,
1096
2-{6-[(tert-butylsulfonyl)amino]-2-methylpyridin-3-yl}-1-[(1S)-1-
cyclopropylethyl]-6-(difluoromethoxy)-5-fluoro-1H-indole-3-
carboxamide, 1097
2-{5-[(tert-butylsulfonyl)amino]pyridin-2-yl}-1-cyclohexyl-6-cyclopro-
pyl- 4-fluoro-1H-indole-3-carboxamide, 1098
6-[3-cyano-6-cyclopropyl-4-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-
- (1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide, 1099
methyl
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-cyclohexyl-5-fluoro-
6-(fluoromethoxy)-1H-indole-3-carboxylate, 1100
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-6-cyclopropyl-5-fluoro--
1- phenyl-1H-indole-3-carboxamide, 1101
N-[5-(3-cyano-6-cyclopropyl-5-fluoro-1-phenyl-1H-indol-2-yl)pyridin-2-
- yl]-2-methylpropane-2-sulfonamide, 1102
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-cyclohexyl-5-fluoro-6-
- (fluoromethoxy)-1H-indole-3-carboxamide, 1103
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-[(1R)-1-cyclopropylet-
hyl]- 6-ethyl-5-fluoro-1H-indole-3-carboxylic acid, 1104
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-[(1R)-1-cyclopropylet-
hyl]- 6-ethyl-5-fluoro-1H-indole-3-carboxamide, 1105
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-6-cyclopropyl-4-fluoro--
1-(4- fluorophenyl)-1H-indole-3-carboxamide, 1106
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-6-ethyl-4-fluoro-1-(4-
fluorophenyl)-1H-indole-3-carboxamide, 1107
6-[3-cyano-5-fluoro-6-(1,1,1-trideuterium)methyl-1-(pyrimidin-2-yl)-1-
H-
indol-2-yl]-N-[(2S)-1,1,1-trifluoro(2-deuterium)propan-2-yl]pyridine-3-
sulfonamide, 1108
N-tert-butyl-6-(3-cyano-5-fluoro-6-methyl-1-phenyl-1H-indol-2-
yl)pyridine-3-sulfonamide, 1109
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-6-ethyl-5-fluoro-1-phenyl-1H--
indole-3-carboxamide, 1110
2-{5-[(tert-butylsulfonyl)amino]pyridin-2-yl}-1-cyclobutyl-6-ethyl-4--
fluoro-1H-indole-3-carboxamide,
1111
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-6-ethyl-4-fluoro-1-phen-
yl-1H- indole-3-carboxamide, 1112
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2-
deuterium)propan-2-yl]pyridine-3-sulfonamide, 1113
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoro(2-deuterium)propan-2-yl]pyridine-3-sulfonamide,
1114
6-[3-cyano-1-cyclobutyl-5-fluoro-6-(1,1,1-trideuterium)methyl-1H-indo-
l-
2-yl]-N-[(2S)-1,1,1-trifluoro(2-deuterium)propan-2-yl]pyridine-3-
sulfonamide, 1115
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclohexyl-5-fluoro-6-methy-
l-1H- indole-3-carboxamide, 1116
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-5-fluoro-6-methyl-1-phenyl-1H-
- indole-3-carboxamide, 1117
N-tert-butyl-6-(3-cyano-6-cyclopropyl-5-fluoro-1-phenyl-1H-indol-2-
yl)pyridine-3-sulfonamide, 1118
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-cyclobutyl-6-ethyl-4--
fluoro-1H-indole-3-carboxamide or 1119
6-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-6-(1,1,1-
trideuterium)methyl-1H-indol-2-yl]-N-[(2-deuterium)propan-2-
yl]pyridine-3-sulfonamide.
In another embodiment of the present invention, a compound of
Formula (I) or a free acid, free base, salt, hydrate, solvate,
clathrate, isotopologue, racemate, enantiomer, diastereomer,
stereoisomer or polymorph form thereof is selected from:
TABLE-US-00002 Cpd Name 7
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-(propan-2-
yl)pyridine-3-sulfonamide, 31
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 35
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 44
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 51
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(propan-
2-yl)pyridine-3-sulfonamide, 107
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-5-fluoro-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 108
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 190
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[1-
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide, 277
N-[6-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)pyridazin-3-
yl]ethanesulfonamide, 300
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 371
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-(1,1,1-trifluoro-2--
methylpropan-2-yl)pyridine-3-sulfonamide, 387
6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 407
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-
difluoropropan-2-yl)pyridine-3-sulfonamide, 408
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 409
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 421
6-(3-cyano-1-cyclobutyl-7-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 512
6-[3-cyano-6-(difluoromethoxy)-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 532
6-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 541
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 549
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 601
6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 634
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 640
6-(3-cyano-1-cyclobutyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-1,1,1--
trifluoropropan-2-yl]pyridine-3-sulfonamide, 650
6-[3-cyano-6-cyclopropyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 657
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(pyridine-2-yl)-1H-indol-2-
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 682
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2--
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 683
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclopentyl-5-fluoro-6-methy-
l- 1H-indole-3-carboxamide, 704
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 716
1-cyclohexyl-5-fluoro-6-methyl-2-(5-{[(2R)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 749
6-[3-cyano-5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indol-2-
yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 810
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-4-methyl-1H-
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
820
6-[3-cyano-6-cyclopropyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 821
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-
1,1,1-trifluorobutan-2-yl]pyridine-3-sulfonamide, 849
6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan--
2- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 937
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(2-methylpropyl)-1H-indol-
2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide,
960
6-[3-cyano-5-fluoro-6-methyl-1-(1,3-thiazol-4-yl)-1H-indol-2-yl]-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 977
6-[3-cyano-5-fluoro-6-methyl-1-(1,3,4-thiadiazol-2-yl)-1H-indol-2-yl]--
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1037
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-cyclohexyl-6-ethyl-5--
fluoro-1H-indole-3-carboxamide, 1064
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-cyclohexyl-6-
(difluoromethoxy)-5-fluoro-1H-indole-3-carboxylic acid, 1065
N-{5-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-
yl]pyridin-2-yl}-2-methylpropane-2-sulfonamide, 1085
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-[(1R)-1-
cyclopropylethyl]-6-(difluoromethoxy)-5-fluoro-1H-indole-3-carboxamide,
1088 2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-cyclohexyl-6-
cyclopropyl-4-fluoro-1H-indole-3-carboxamide, 1092
N-[6-(3-cyano-1-cyclohexyl-6-cyclopropyl-4-fluoro-1H-indol-2-
yl)pyridin-3-yl]-2-methylpropane-2-sulfonamide, 1100
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-6-cyclopropyl-5-fluoro--
1- phenyl-1H-indole-3-carboxamide, 1110
2-{5-[(tert-butylsulfonyl)amino]pyridin-2-yl}-1-cyclobutyl-6-ethyl-4--
fluoro-1H-indole-3-carboxamide or 1111
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-6-ethyl-4-fluoro-1-phen-
yl- 1H-indole-3-carboxamide.
In another embodiment of the present invention, a compound of
Formula (I) or a free acid, free base, salt, hydrate, solvate,
clathrate, isotopologue, racemate, enantiomer, diastereomer,
stereoisomer or polymorph form thereof is selected from:
TABLE-US-00003 Cpd Name 300
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 387
6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 409
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2R)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 512
6-[3-cyano-6-(difluoromethoxy)-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 541
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 549
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 601
6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide, 634
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-
- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 650
6-[3-cyano-6-cyclopropyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 682
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2--
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 704
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)--
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 820
6-[3-cyano-6-cyclopropyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N--
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 849
6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-2-(5-{[(2S)-1,1,1-trifluoropropan--
2- yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide, 960
6-[3-cyano-5-fluoro-6-methyl-1-(1,3-thiazol-4-yl)-1H-indol-2-yl]-N-
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide, 1037
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-cyclohexyl-6-ethyl-5--
fluoro-1H-indole-3-carboxamide, 1064
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-cyclohexyl-6-
(difluoromethoxy)-5-fluoro-1H-indole-3-carboxylic acid, 1065
N-{5-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-
yl]pyridin-2-yl}-2-methylpropane-2-sulfonamide, 1088
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-cyclohexyl-6-
cyclopropyl-4-fluoro-1H-indole-3-carboxamide or 1100
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-6-cyclopropyl-5-fluoro--
1- phenyl-1H-indole-3-carboxamide.
Chemical Definitions
The chemical terms used above and throughout the description of the
invention, unless specifically defined otherwise, shall be
understood by one of ordinary skill in the art to have the
following indicated meanings.
As used herein, the term "C.sub.1-8alkyl" generally refers to
saturated hydrocarbon radicals having from one to eight carbon
atoms in a straight or branched chain configuration, including
methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl,
tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl and the like. In
some embodiments, C.sub.1-8alkyl includes C.sub.1-6alkyl,
C.sub.1-4alkyl and the like. A C.sub.1-8alkyl radical may be
optionally substituted where allowed by available valences.
As used herein, the term "C.sub.2-8alkenyl" generally refers to
partially unsaturated hydrocarbon radicals having from two to eight
carbon atoms in a straight or branched chain configuration and one
or more carbon-carbon double bonds therein, including ethenyl,
allyl, propenyl and the like. In some embodiments, C.sub.2-8alkenyl
includes C.sub.2-6alkenyl, C.sub.2-4alkenyl and the like. A
C.sub.2-8alkenyl radical may be optionally substituted where
allowed by available valences.
As used herein, the term "C.sub.1-8alkoxy" generally refers to
saturated hydrocarbon radicals having from one to eight carbon
atoms in a straight or branched chain configuration of the formula:
--O--C.sub.1-8alkyl, including methoxy, ethoxy, n-propoxy,
isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy,
n-pentoxy, n-hexoxy and the like. In some embodiments,
C.sub.1-8alkoxy includes C.sub.1-6alkoxy, C.sub.1-4alkoxy and the
like. A C.sub.1-8alkoxy radical may be optionally substituted where
allowed by available valences.
As used herein, the term "C.sub.3-14cycloalkyl" generally refers to
a saturated monocyclic, bicyclic or polycyclic hydrocarbon radical,
including cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,
cycloheptyl, cyclooctyl, 1H-indanyl, indenyl,
tetrahydro-naphthalenyl and the like. In some embodiments,
C.sub.3-14cycloalkyl includes C.sub.3-8cycloalkyl,
C.sub.5-8cycloalkyl, C.sub.3-10cycloalkyl and the like. A
C.sub.3-14cycloalkyl radical may be optionally substituted where
allowed by available valences.
As used herein, the term "C.sub.3-14cycloalkenyl" generally refers
to a partially unsaturated monocyclic, bicyclic or polycyclic
hydrocarbon radical having one or more chemically stable
carbon-carbon double bonds therein, including cyclopropenyl,
cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl,
cyclooctenyl and the like. In some embodiments,
C.sub.3-14cycloalkenyl includes C.sub.3-8cycloalkenyl,
C.sub.5-8cycloalkenyl, C.sub.3-10cycloalkenyl and the like. A
C.sub.3-14cycloalkenyl radical may be optionally substituted where
allowed by available valences.
As used herein, the term "aryl" generally refers to a monocyclic,
bicyclic or polycyclic aromatic carbon atom ring structure radical,
including phenyl, naphthyl, anthracenyl, fluorenyl, azulenyl,
phenanthrenyl and the like. An aryl radical may be optionally
substituted where allowed by available valences.
As used herein, the term "heteroaryl" generally refers to a
monocyclic, bicyclic or polycyclic aromatic carbon atom ring
structure radical in which one or more carbon atom ring members
have been replaced, where allowed by structural stability, with one
or more heteroatoms, such as an O, S or N atom, including furanyl,
thienyl (or thiophenyl), 2H-pyrrolyl, 3H-pyrrolyl, pyrazolyl,
imidazolyl, isoxazolyl, isothiazolyl, oxazolyl, thiazolyl,
triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyranyl,
thiopyranyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl,
triazinyl, indole, indazolyl, isoindolyl, benzofuranyl,
benzothienyl, benzimidazolyl, benzoxazolyl, purinyl, quinolinyl,
isoquinolinyl, quinazolinyl, quinoxalinyl, 1,3-diazinyl,
1,2-diazinyl, 1,2-diazolyl, 1,4-diazanaphthalenyl, acridinyl and
the like. A heteroaryl radical may be optionally substituted on a
carbon or nitrogen atom ring member where allowed by available
valences.
As used herein, the term "heterocyclyl" generally refers to a
saturated or partially unsaturated monocyclic, bicyclic or
polycyclic carbon atom ring structure radical in which one or more
carbon atom ring members have been replaced, where allowed by
structural stability, with a heteroatom, such as an O, S or N atom,
including oxiranyl, oxetanyl, azetidinyl, dihydrofuranyl,
tetrahydrofuranyl, dihydrothienyl, tetrahydrothienyl, pyrrolinyl,
pyrrolidinyl, dihydropyrazolyl, pyrazolinyl, pyrazolidinyl,
dihydroimidazolyl, imidazolinyl, imidazolidinyl, isoxazolinyl,
isoxazolidinyl, isothiazolinyl, isothiazolidinyl, oxazolinyl,
oxazolidinyl, thiazolinyl, thiazolidinyl, triazolinyl,
triazolidinyl, oxadiazolinyl, oxadiazolidinyl, thiadiazolinyl,
thiadiazolidinyl, tetrazolinyl, tetrazolidinyl, dihydro-2H-pyranyl,
tetrahydro-2H-pyranyl, tetrahydro-thiopyranyl, dihydro-pyridinyl,
tetrahydro-pyridinyl, hexahydro-pyridinyl, dihydro-pyrimidinyl,
tetrahydro-pyrimidinyl, dihydro-pyrazinyl, tetrahydro-pyrazinyl,
dihydro-pyridazinyl, tetrahydro-pyridazinyl, piperazinyl,
piperidinyl, morpholinyl, thiomorpholinyl, dihydro-triazinyl,
tetrahydro-triazinyl, hexahydro-triazinyl, dihydro-indole,
tetrahydro-indole, dihydro-indazolyl, tetrahydro-indazolyl,
dihydro-isoindolyl, tetrahydro-isoindolyl, dihydro-benzofuranyl,
tetrahydro-benzofuranyl, dihydro-benzothienyl,
tetrahydro-benzothienyl, dihydro-benzimidazolyl,
tetrahydro-benzimidazolyl, dihydro-benzoxazolyl,
tetrahydro-benzoxazolyl, benzo[1,3]dioxolyl, benzo[1,4]dioxanyl,
dihydro-purinyl, tetrahydro-purinyl, dihydro-quinolinyl,
tetrahydro-quinolinyl, dihydro-isoquinolinyl,
tetrahydro-isoquinolinyl, dihydro-quinazolinyl,
tetrahydro-quinazolinyl, dihydro-quinoxalinyl,
tetrahydro-quinoxalinyl and the like. A heterocyclyl radical may be
optionally substituted on a carbon or nitrogen atom ring member
where allowed by available valences.
As used herein, the term "C.sub.2-8alkenyl-C.sub.1-8alkyl" refers
to a radical of the formula: --C.sub.1-8alkyl-C.sub.2-8alkenyl.
As used herein, the term "C.sub.1-8alkoxy-C.sub.1-8alkyl" refers to
a radical of the formula: --C.sub.1-8alkyl-O--C.sub.1-8alkyl.
As used herein, the term
"C.sub.1-8alkoxy-C.sub.1-8alkyl-amino-C.sub.1-8alkoxy" refers to a
radical of the formula:
--O--C.sub.1-8alkyl-NH--C.sub.1-8alkyl-O--C.sub.1-8alkyl or
--O--C.sub.1-8alkyl-N(C.sub.1-8alkyl-O--C.sub.1-8alkyl).sub.2.
As used herein, the term "C.sub.1-8alkoxy-carbonyl" refers to a
radical of the formula: --C(O)--O--C.sub.1-8alkyl.
As used herein, the term "C.sub.1-8alkoxy-carbonyl-C.sub.1-8alkyl"
refers to a radical of the formula:
--C.sub.1-8alkyl-C(O)--O--C.sub.1-8alkyl.
As used herein, the term "C.sub.1-8alkoxy-carbonyl-amino" refers to
a radical of the formula: --NH--C(O)--O--C.sub.1-8alkyl.
As used herein, the term "C.sub.1-8alkyl-amino" refers to a radical
of the formula: --NH--C.sub.1-8alkyl or
--N(C.sub.1-8alkyl).sub.2.
As used herein, the term "C.sub.1-8alkyl-amino-C.sub.1-8alkoxy"
refers to a radical of the formula:
--O--C.sub.1-8alkyl-NH--C.sub.1-8alkyl or
--C.sub.1-8alkyl-N(C.sub.1-8alkyl).sub.2.
As used herein, the term "C.sub.1-8alkyl-amino-C.sub.1-8alkyl"
refers to a radical of the formula:
--C.sub.1-8alkyl-NH--C.sub.1-8alkyl or
--C.sub.1-8alkyl-N(C.sub.1-8alkyl).sub.2.
As used herein, the term
"C.sub.1-8alkyl-amino-C.sub.1-8alkyl-amino-C.sub.1-8alkoxy" refers
to a radical of the formula:
--O--C.sub.1-8alkyl-NH--C.sub.1-8alkyl-NH--C.sub.1-8alkyl or
--O--C.sub.1-8alkyl-N(C.sub.1-8alkyl-NH--C.sub.1-8alkyl).sub.2.
As used herein, the term "C.sub.1-8alkyl-amino-carbonyl" refers to
a radical of the formula: --C(O)--NH--C.sub.1-8alkyl or
--C(O)--N(C.sub.1-8alkyl).sub.2.
As used herein, the term "C.sub.1-8alkyl-amino-carbonyl-amino"
refers to a radical of the formula: --NH--C(O)--NH--C.sub.1-8alkyl
or --NH--C(O)--N(C.sub.1-8alkyl).sub.2.
As used herein, the term "C.sub.1-8alkyl-carbonyl" refers to a
radical of the formula: --C(O)--C.sub.1-8alkyl.
As used herein, the term "C.sub.1-8alkyl-carbonyloxy" refers to a
radical of the formula: --O--C(O)--C.sub.1-8alkyl.
As used herein, the term
"C.sub.1-8alkyl-carbonyloxy-C.sub.1-8alkoxy" refers to a radical of
the formula: --O--C.sub.1-8alkyl-O--C(O)--C.sub.1-8alkyl.
As used herein, the term
"C.sub.1-8alkyl-carbonyloxy-C.sub.1-8alkyl" refers to a radical of
the formula: --C.sub.1-8alkyl-O--C(O)--C.sub.1-8alkyl.
As used herein, the term "C.sub.1-8alkyl-sulfinyl" refers to a
radical of the formula: --SO--C.sub.1-8alkyl.
As used herein, the term "C.sub.1-8alkyl-sulfonyl" refers to a
radical of the formula: --SO.sub.2--C.sub.1-8alkyl.
As used herein, the term "amino-sulfonyl" refers to a radical of
the formula: --SO.sub.2--NH.sub.2.
As used herein, the term "C.sub.1-8alkyl-sulfonyl-amino" refers to
a radical of the formula: --NH--SO.sub.2--C.sub.1-8alkyl.
As used herein, the term "C.sub.1-8alkylthio" refers to a radical
of the formula: --S--C.sub.1-8alkyl.
As used herein, the term "C.sub.2-8alkynyl-C.sub.1-8alkyl" refers
to a radical of the formula: --C.sub.1-8alkyl-C.sub.2-8alkynyl.
As used herein, the term "amino" refers to a radical of the
formula: --NH.sub.2.
As used herein, the term "amino-C.sub.1-8alkoxy" refers to a
radical of the formula: --O--C.sub.1-8alkyl-NH.sub.2.
As used herein, the term "amino-C.sub.1-8alkyl" refers to a radical
of the formula: --C.sub.1-8alkyl-NH.sub.2.
As used herein, the term
"amino-C.sub.1-8alkyl-amino-C.sub.1-8alkoxy" refers to a radical of
the formula: --O--C.sub.1-8alkyl-NH--C.sub.1-8alkyl-NH.sub.2 or
--O--C.sub.1-8alkyl-N(C.sub.1-8alkyl-NH.sub.2).sub.2.
As used herein, the term "amino-carbonyl" refers to a radical of
the formula: --C(O)--NH.sub.2.
As used herein, the term "amino-carbonyl-amino" refers to a radical
of the formula: --NH--C(O)--NH.sub.2.
As used herein, the term "aryl-C.sub.1-8alkoxy" refers to a radical
of the formula: --O--C.sub.1-8alkyl-aryl.
As used herein, the term "aryl-C.sub.1-8alkyl" refers to a radical
of the formula: --C.sub.1-8alkyl-aryl.
As used herein, the term "aryl-carbonyl-amino" refers to a radical
of the formula: --NH--C(O)-aryl.
As used herein, the term "aryloxy" refers to a radical of the
formula: --O-aryl.
As used herein, the term "carboxyl" refers to a radical of the
formula: --COOH, --C(O)OH or --CO.sub.2H.
As used herein, the term "carboxyl-amino" refers to a radical of
the formula: --NH--COOH, --NH--C(O)OH or --NH--CO.sub.2H.
As used herein, the term "cyano-C.sub.1-8alkyl" refers to a radical
of the formula: --C.sub.1-8alkyl-CN.
As used herein, the term "1-cyano-ethyl" refers to a radical of the
formula: --CH(CN)--CH.sub.3.
As used herein, the term "C.sub.3-14cycloalkyl-C.sub.1-8alkoxy"
refers to a radical of the formula:
--O--C.sub.1-8alkyl-C.sub.3-14cycloalkyl.
As used herein, the term "C.sub.3-14cycloalkyl-C.sub.1-8alkyl"
refers to a radical of the formula:
--C.sub.1-8alkyl-C.sub.3-14cycloalkyl.
As used herein, the term "C.sub.3-14cycloalkyloxy" refers to a
radical of the formula: --O--C.sub.3-14cycloalkyl.
As used herein, the term "1-cyclopropyl-ethyl" refers to a radical
of the formula: --CH(cyclopropyl)-CH.sub.3.
As used herein, the term "cyclopropyl-methyl" refers to a radical
of the formula: --CH.sub.2-cyclopropyl.
As used herein, the term "formyl" refers to a radical of the
formula: --C(O)--H
As used herein, the term "halo" or "halogen" generally refers to a
halogen atom radical, including fluoro, chloro, bromo and iodo.
As used herein, the term "halo-C.sub.2-8alkenyl" refers to a
radical of the formula: --C.sub.2-8alkenyl-halo, wherein
C.sub.2-8alkenyl may be partially or completely substituted where
allowed by available valences with one or more halogen atoms,
including fluoroethenyl, difluoroethenyl or difluoroallyl and the
like. In some embodiments, difluoroethenyl includes
2,2-difluorovinyl or 1,2-difluorovinyl and the like; difluoroallyl
includes 1,1-difluoroallyl and the like. In some embodiments,
halo-C.sub.2-8alkenyl includes halo-C.sub.2-8alkenyl,
halo-C.sub.2-4alkenyl and the like.
As used herein, the term "halo-C.sub.1-8alkoxy" refers to a radical
of the formula: --O--C.sub.1-8alkyl-halo, wherein C.sub.1-8alkyl
may be partially or completely substituted where allowed by
available valences with one or more halogen atoms, including
fluoromethoxy, difluoromethoxy, trifluoromethoxy, fluoroethoxy,
difluoroethoxy or trifluoroethoxy and the like. In some
embodiments, difluoroethoxy includes 2,2-difluoroethoxy,
1,2-difluoroethoxy or 1,1-difluoroethoxy and the like. In some
embodiments, halo-C.sub.1-8alkoxy includes halo-C.sub.1-6alkoxy,
halo-C.sub.1-4alkoxy and the like.
As used herein, the term "halo-C.sub.1-8alkyl" refers to a radical
of the formula: --C.sub.1-8alkyl-halo, wherein C.sub.1-8alkyl may
be partially or completely substituted where allowed by available
valences with one or more halogen atoms, including fluoromethyl,
difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl,
trifluoroethyl, fluoroisopropyl, difluoroisopropyl,
trifluoroisopropyl, fluoro-tert-butyl, difluoro-tert-butyl,
trifluoro-tert-butyl and the like. In some embodiments,
difluoroethyl includes 2,2-difluoroethyl, 1,2-difluoroethyl or
1,1-difluoroethyl and the like; difluoroisopropyl includes
1,3-difluoropropan-2-yl and the like; trifluoroisopropyl includes
1,1,1-trifluoropropan-2-yl and the like; trifluoro-tert-butyl
includes 1,1,1-trifluoro-2-methylpropan-2-yl and the like. In some
embodiments, halo-C.sub.1-8alkyl includes halo-C.sub.1-6alkyl,
halo-C.sub.1-4alkyl and the like.
As used herein, the term "heteroaryl-C.sub.1-8alkoxy" refers to a
radical of the formula: --O--C.sub.1-8alkyl-heteroaryl.
As used herein, the term "heteroaryl-C.sub.1-8alkyl" refers to a
radical of the formula: --C.sub.1-8alkyl-heteroaryl.
As used herein, the term "heteroaryloxy" refers to a radical of the
formula: --O-heteroaryl.
As used herein, the term "heterocyclyl-C.sub.1-8alkoxy" refers to a
radical of the formula: --O--C.sub.1-8alkyl-heterocyclyl.
As used herein, the term "heterocyclyl-C.sub.1-8alkyl" refers to a
radical of the formula: --C.sub.1-8alkyl-heterocyclyl.
As used herein, the term "heterocyclyl-carbonyloxy" refers to a
radical of the formula: --O--C(O)-heterocyclyl.
As used herein, the term "heterocyclyloxy" refers to a radical of
the formula: --O-heterocyclyl.
As used herein, the term "hydroxy-C.sub.1-8alkyl" refers to a
radical of the formula: --C.sub.1-8alkyl-OH, wherein C.sub.1-8alkyl
may be partially or completely substituted where allowed by
available valences with one or more hydroxy radicals.
As used herein, the term "substituent" means positional variables
on the atoms of a core molecule that are substituted at a
designated atom position, replacing one or more hydrogens on the
designated atom, provided that the designated atom's normal valency
is not exceeded, and that the substitution results in a stable
compound. Combinations of substituents and/or variables are
permissible only if such combinations result in stable compounds.
It should also be noted that any carbon as well as heteroatom with
valences that appear to be unsatisfied as described or shown herein
is assumed to have a sufficient number of hydrogen atom(s) to
satisfy the valences described or shown.
For the purposes of this invention, where one or more substituent
variables for a compound of Formula (I) encompass functionalities
incorporated into a compound of Formula (I), each functionality
appearing at any location within the disclosed compound may be
independently selected, and as appropriate, independently and/or
optionally substituted.
As used herein, the terms "independently selected," or "each
selected" refer to functional variables in a substituent list that
may occur more than once on the structure of Formula (I) or Formula
(Ia), the pattern of substitution at each occurrence is independent
of the pattern at any other occurrence. Further, the use of a
generic substituent variable on any formula or structure for a
compound of the present invention is understood to include the
replacement of the generic substituent with species substituents
that are included within the particular genus, e.g., aryl may be
replaced with phenyl or naphthalenyl and the like, and that the
resulting compound is to be included within the scope of the
compounds representative of the present invention.
As used herein, the term "each instance of" when used in a phrase
such as " . . . aryl, aryl-C.sub.1-8alkyl, heterocyclyl and
heterocyclyl-C.sub.1-8alkyl, wherein each instance of aryl and
heterocyclyl is optionally substituted with one or two substituents
. . . " is intended to include optional, independent substitution
on each of the aryl and heterocyclyl rings and on the aryl and
heterocyclyl portions of aryl-C.sub.1-8alkyl and
heterocyclyl-C.sub.1-8alkyl.
As used herein, the term "optionally substituted" means optional
substitution with the specified substituent variables, groups,
radicals or moieties.
As used herein, the terms "stable compound" or "stable structure"
mean a compound that is sufficiently robust to survive isolation to
a useful degree of purity from a reaction mixture and formulations
thereof into an efficacious therapeutic agent.
Compound names used herein were obtained using ACD Labs Index Name
software Version 10.0, provided by ACD Labs; and/or, were provided
using the Autonom function of Chem Draw Ultra 10.0.4, provided by
CambridgeSoft. When the compound name disclosed herein conflicts
with the structure depicted, the structure shown will supercede the
use of the name to define the compound intended.
Compound Forms
As used herein, the term "form" means a compound of Formula (I), or
Formula (Ia) isolated for use selected from a free acid, free base,
salt, hydrate, solvate, clathrate, isotopologue, racemate,
enantiomer, diastereomer, stereoisomer, polymorph or tautomer form
thereof.
As used herein, the term "isolated" means the physical state of a
compound of Formula (I), or Formula (Ia) after being isolated
and/or purified from a synthetic process (e.g., from a reaction
mixture) or natural source or combination thereof according to an
isolation or purification process or processes described herein or
which are well known to the skilled artisan (e.g., chromatography,
recrystallization and the like) in sufficient purity to be
characterizable by standard analytical techniques described herein
or well known to the skilled artisan.
As used herein, the term "protected" means that a functional group
in a compound of Formula (I) is in a form modified to preclude
undesired side reactions at the protected site when the compound is
subjected to a reaction. Suitable protecting groups will be
recognized by those with ordinary skill in the art as well as by
reference to standard textbooks such as, for example, T. W. Greene
et al, Protective Groups in organic Synthesis (1991), Wiley, New
York.
Prodrugs and solvates of the compounds of the invention are also
contemplated herein.
As used herein, the term "prodrug" means a form of an instant
compound (e.g., a drug precursor) that is transformed in vivo to
yield an active compound of Formula (I) or a form thereof. The
transformation may occur by various mechanisms (e.g., by metabolic
and/or non-metabolic chemical processes), such as, for example,
through hydrolysis and/or metabolism in blood, liver and/or other
organs and tissues. A discussion of the use of prodrugs is provided
by T. Higuchi and W. Stella, "Pro-drugs as Novel Delivery Systems,"
Vol. 14 of the A.C.S. Symposium Series, and in Bioreversible
Carriers in Drug Design, ed. Edward B. Roche, American
Pharmaceutical Association and Pergamon Press, 1987.
In one example, when a compound of Formula (I) or a form thereof
contains a carboxylic acid functional group, a prodrug can comprise
an ester formed by the replacement of the hydrogen atom of the acid
group with a functional group such as alkyl and the like. In
another example, when a compound of Formula (I) or a form thereof
contains an alcohol functional group, a prodrug can be formed by
the replacement of the hydrogen atom of the alcohol group with a
functional group such as alkyl or carbonyloxy and the like. In
another example, when a compound of Formula (I) or a form thereof
contains an amine functional group, a prodrug can be formed by the
replacement of one or more amine hydrogen atoms with a functional
group such as alkyl or substituted carbonyl.
One or more compounds of the invention may exist in unsolvated as
well as solvated forms with pharmaceutically acceptable solvents
such as water, ethanol, and the like, and it is intended that the
invention embrace both solvated and unsolvated forms.
As used herein, the term "solvate" means a physical association of
a compound of this invention with one or more solvent molecules.
This physical association involves varying degrees of ionic and
covalent bonding, including hydrogen bonding. In certain instances
the solvate will be capable of isolation, for example when one or
more solvent molecules are incorporated in the crystal lattice of
the crystalline solid. As used herein, "solvate" encompasses both
solution-phase and isolatable solvates. Non-limiting examples of
suitable solvates include ethanolates, methanolates, and the
like.
One or more compounds of the invention may optionally be converted
to a solvate. Preparation of solvates is generally known. The
preparation of solvates of the antifungal fluconazole in ethyl
acetate as well as from water has been described (see, M. Caira et
al, J. Pharmaceutical Sci., 93(3), 601-611 (2004)). Similar
preparations of solvates, hemisolvate, hydrates and the like have
also been described (see, E. C. van Tonder et al, AAPS
PharmSciTech., 5(1), article 12 (2004); and A. L. Bingham et al,
Chem. Commun., 603-604 (2001)). A typical, non-limiting process
involves dissolving a compound in a desired amount of the desired
solvent (organic or water or mixtures thereof) at a higher than
ambient temperature, and cooling the solution at a rate sufficient
to form crystals which are then isolated by standard methods.
Analytical techniques such as, for example infrared spectroscopy,
show the presence of the solvent (or water) in the crystals as a
solvate (or hydrate).
As used herein, the term "hydrate" means a solvate wherein the
solvent molecule is water.
The compounds of Formula (I) can form salts which are also within
the scope of this invention. Reference to a compound of Formula (I)
herein is understood to include reference to salts thereof, unless
otherwise indicated. The term "salt(s)", as employed herein,
denotes acidic salts formed with inorganic and/or organic acids, as
well as basic salts formed with inorganic and/or organic bases. In
addition, when a compound of Formula (I) contains both a basic
moiety, such as, but not limited to a pyridine or imidazole, and an
acidic moiety, such as, but not limited to a carboxylic acid,
zwitterions ("inner salts") may be formed and are included within
the term "salt(s)" as used herein.
Pharmaceutically acceptable (i.e., non-toxic, physiologically
acceptable) salts are preferred, although other salts are also
useful. Salts of the compounds of the Formula (I) may be formed,
for example, by reacting a compound of Formula (I) with an amount
of acid or base, such as an equivalent amount, in a medium such as
one in which the salt precipitates or in an aqueous medium followed
by lyophilization.
Exemplary acid addition salts include acetates, ascorbates,
benzoates, benzenesulfonates, bisulfates, borates, butyrates,
citrates, camphorates, camphorsulfonates, fumarates,
hydrochlorides, hydrobromides, hydroiodides, lactates, maleates,
methanesulfonates, naphthalenesulfonates, nitrates, oxalates,
phosphates, propionates, salicylates, succinates, sulfates,
tartarates, thiocyanates, toluenesulfonates (also known as
tosylates,) and the like.
Additionally, acids which are generally considered suitable for the
formation of pharmaceutically useful salts from basic
pharmaceutical compounds are discussed, for example, by P. Stahl et
al, Camille G. (eds.) Handbook of Pharmaceutical Salts. Properties,
Selection and Use. (2002) Zurich: Wiley-VCH; S. Berge et al,
Journal of Pharmaceutical Sciences (1977) 66(1) 1-19; P. Gould,
International J. of Pharmaceutics (1986) 33, 201-217; Anderson et
al, The Practice of Medicinal Chemistry (1996), Academic Press, New
York; and in The Orange Book (Food & Drug Administration,
Washington, D.C. on their website). These disclosures are
incorporated herein by reference thereto.
Exemplary basic salts include ammonium salts, alkali metal salts
such as sodium, lithium, and potassium salts, alkaline earth metal
salts such as calcium and magnesium salts, salts with organic bases
(for example, organic amines) such as dicyclohexylamines, t-butyl
amines, and salts with amino acids such as arginine, lysine and the
like. Basic nitrogen-containing groups may be quarternized with
agents such as lower alkyl halides (e.g. methyl, ethyl, and butyl
chlorides, bromides and iodides), dialkyl sulfates (e.g. dimethyl,
diethyl, and dibutyl sulfates), long chain halides (e.g. decyl,
lauryl, and stearyl chlorides, bromides and iodides), aralkyl
halides (e.g. benzyl and phenethyl bromides), and others.
All such acid salts and base salts are intended to be
pharmaceutically acceptable salts within the scope of the invention
and all acid and base salts are considered equivalent to the free
forms of the corresponding compounds for purposes of the
invention.
Pharmaceutically acceptable esters of the present compounds include
the following groups: carboxylic acid esters, sulfonate esters,
amino acid esters phosphonate esters and mono-, di- or triphosphate
esters.
Compounds of Formula I, and salts, solvates, esters and prodrugs
thereof, may further exist in their tautomeric form (for example,
as an amide or imino ether). All such tautomeric forms are
contemplated herein as part of the present invention.
The compounds of Formula (I) may contain asymmetric or chiral
centers, and, therefore, exist in different stereoisomeric forms.
It is intended that all stereoisomeric forms of the compounds of
Formula (I) as well as mixtures thereof, including racemic
mixtures, form part of the present invention.
The compounds of the invention may include one or more chiral
centers, and as such may exist as racemic mixtures (R/S) or as
substantially pure enantiomers and diastereomers. The compounds may
also exist as substantially pure (R) or (S) enantiomers (when one
chiral center is present). In one embodiment, the compounds of the
invention are (S) isomers and may exist as enantiomerically pure
compositions substantially comprising only the (S) isomer. In
another embodiment, the compounds of the invention are (R) isomers
and may exist as enantiomerically pure compositions substantially
comprising only the (R) isomer. As one of skill in the art will
recognize, when more than one chiral center is present, the
compounds of the invention may also exist as a (R,R), (R,S), (S,R)
or (S,S) isomer, as defined by IUPAC Nomenclature
Recommendations.
As used herein, the term "substantially pure" refers to compounds
consisting substantially of a single isomer in an amount greater
than or equal to 90%, in an amount greater than or equal to 92%, in
an amount greater than or equal to 95%, in an amount greater than
or equal to 98%, in an amount greater than or equal to 99%, or in
an amount equal to 100% of the single isomer.
In one aspect of the invention, a compound of Formula (I) is a
substantially pure (S) enantiomer present in an amount greater than
or equal to 90%, in an amount greater than or equal to 92%, in an
amount greater than or equal to 95%, in an amount greater than or
equal to 98%, in an amount greater than or equal to 99%, or in an
amount equal to 100%.
In one aspect of the invention, a compound of Formula (I) is a
substantially pure (R) enantiomer present in an amount greater than
or equal to 90%, in an amount greater than or equal to 92%, in an
amount greater than or equal to 95%, in an amount greater than or
equal to 98%, in an amount greater than or equal to 99%, or in an
amount equal to 100%.
As used herein, a "racemate" is any mixture of isometric forms that
are not "enantiomerically pure", including mixtures such as,
without limitation, in a ratio of about 50/50, about 60/40, about
70/30, or about 80/20.
In addition, the present invention embraces all geometric and
positional isomers. For example, if a compound of Formula (I)
incorporates a double bond or a fused ring, both the cis- and
trans-forms, as well as mixtures, are embraced within the scope of
the invention. Diastereomeric mixtures can be separated into their
individual diastereomers on the basis of their physical chemical
differences by methods well known to those skilled in the art, such
as, for example, by chromatography and/or fractional
crystallization. Enantiomers can be separated by use of chiral HPLC
column or other chromatographic methods known to those skilled in
the art. Enantiomers can also be separated by converting the
enantiomeric mixture into a diastereomeric mixture by reaction with
an appropriate optically active compound (e.g., chiral auxiliary
such as a chiral alcohol or Mosher's acid chloride), separating the
diastereomers and converting (e.g., hydrolyzing) the individual
diastereomers to the corresponding pure enantiomers. Also, some of
the compounds of Formula (I) may be atropisomers (e.g., substituted
biaryls) and are considered as part of this invention.
It is also possible that the compounds of Formula (I) may exist in
different tautomeric forms, and all such forms are embraced within
the scope of the invention. Also, for example, all keto-enol and
imine-enamine forms of the compounds are included in the
invention.
All stereoisomers (for example, geometric isomers, optical isomers
and the like) of the present compounds (including those of the
salts, solvates, esters and prodrugs of the compounds as well as
the salts, solvates and esters of the prod rugs), such as those
which may exist due to asymmetric carbons on various substituents,
including enantiomeric forms (which may exist even in the absence
of asymmetric carbons), rotameric forms, atropisomers, and
diastereomeric forms, are contemplated within the scope of this
invention, as are positional isomers (such as, for example,
4-pyridyl and 3-pyridyl). For example, if a compound of Formula (I)
incorporates a double bond or a fused ring, both the cis- and
trans-forms, as well as mixtures thereof, are embraced within the
scope of the invention. Also, for example, all keto-enol and
imine-enamine forms of the compounds are included in the invention.
Individual stereoisomers of the compounds of the invention may, for
example, be substantially free of other isomers, or may be present
in a racemic mixture, as described supra.
The use of the terms "salt", "solvate", "ester", "prodrug" and the
like, is intended to equally apply to the salt, solvate, ester and
prodrug of enantiomers, stereoisomers, rotamers, tautomers,
positional isomers, racemates, isotopologues or prodrugs of the
instant compounds.
The term "isotopologue" refers to isotopically-enriched compounds
of the present invention which are identical to those recited
herein, but for the fact that one or more atoms are replaced by an
atom having an atomic mass or mass number different from the atomic
mass or mass number usually found in nature. Examples of isotopes
that can be incorporated into compounds of the invention include
isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus,
fluorine and chlorine, such as H.sup.2, H.sup.3, C.sup.13,
C.sup.14, N.sup.15, O.sup.18, O.sup.17, P.sup.31, P.sup.32,
S.sup.35, F.sup.18, Cl.sup.35 and Cl.sup.36, respectively, each of
which are also within the scope of this invention.
Certain isotopically-enriched compounds of the present invention
(e.g., those labeled with H.sup.3 and C.sup.14) are useful in
compound and/or substrate tissue distribution assays. Tritiated
(i.e., H.sup.3) and carbon-14 (i.e., C.sup.14) isotopes are
particularly preferred for their ease of preparation and
detectability. Further, substitution with heavier isotopes such as
deuterium (i.e., H.sup.2) may afford certain therapeutic advantages
resulting from greater metabolic stability (e.g., increased in vivo
half-life or reduced dosage requirements) and hence may be
preferred in some circumstances. Isotopically-enriched compounds of
Formula (I) can generally be prepared by following procedures
analogous to those disclosed in the Schemes and/or in the Examples
hereinbelow, by substituting an appropriate isotopically-enriched
reagent for a non-isotopically-enriched reagent.
When the compounds are enriched with deuterium, the
deuterium-to-hydrogen ratio in the deuterated areas of the
molecules substantially exceeds the naturally occurring
deuterium-to-hydrogen ratio. Wikipedia
(http://en.wikipedia.org/wiki/Deuterium) suggests that deuterium
has a natural abundance in the oceans of Earth of approximately one
atom in 6500 of hydrogen (.about.154 PPM). Deuterium thus accounts
for approximately 0.015% (on a weight basis, 0.030%) of all
naturally occurring hydrogen in the oceans on Earth. However, other
sources suggest a much higher abundance of e.g. 610.sup.-4 (6 atoms
in 10,000 or 0.06% atom basis).
Polymorphic crystalline and amorphous forms of the compounds of
Formula (I), and of the salts, solvates, esters and prodrugs of the
compounds of Formula (I), are further intended to be included in
the present invention.
Use of the Invention
The present invention is directed to compounds useful for treating
or ameliorating a viral infection by modulating viral replication.
In accordance with the present invention, compounds that modulate
HCV viral replication have been identified and methods of using
these compounds for treating or ameliorating HCV infection or
disorders or symptoms associated therewith are provided.
One embodiment of the present invention is directed to a method for
treating a viral infection in a subject in need thereof comprising
administering an effective amount of a compound of Formula (I) or a
form thereof to the subject.
An embodiment of the present invention includes the use of a
compound of Formula (I) or a form thereof in the manufacture of a
medicament for treating a viral infection in a subject in need
thereof comprising administering an effective amount of the
medicament to the subject.
An embodiment of the present invention includes the use of a
compound of Formula (I) or a form thereof in the preparation of a
pharmaceutical kit comprising the compound of Formula (I) or a form
thereof and instructions for administering the compound for
treating a viral infection in a subject in need thereof.
For each of such embodiments for treating a viral infection in a
subject in need thereof, the use of a compound of Formula (I) or a
form thereof further includes a use of the compound of Formula (Ia)
or a form thereof.
Another embodiment of the present invention is directed to the use
of a compound of Formula (I) or Formula (Ia) or a form thereof for
treating a viral infection by inhibiting viral replication.
An embodiment of the present invention includes the use of a
compound of Formula (I) or Formula (Ia) or a form thereof for
treating or ameliorating HCV infection or disorders or symptoms
associated therewith by inhibiting Hepatitis C viral
replication.
An embodiment of the present invention includes a method for
treating or ameliorating HCV infection or disorders or symptoms
associated therewith in a subject in need thereof comprising
administering an effective amount of a compound of Formula (I) or a
form thereof to the subject.
An embodiment of the present invention includes the use of a
compound of Formula (I) or a form thereof in the manufacture of a
medicament for treating or ameliorating HCV infection or disorders
or symptoms associated therewith in a subject in need thereof
comprising administering an effective amount of the medicament to
the subject.
An embodiment of the present invention includes the use of a
compound of Formula (I) or a form thereof in the preparation of a
pharmaceutical kit comprising the compound of Formula (I) or a form
thereof and instructions for administering the compound for
treating or ameliorating HCV infection or disorders or symptoms
associated therewith in a subject in need thereof.
For each of such embodiments for treating or ameliorating HCV
infection or disorders or symptoms associated therewith in a
subject in need thereof, the use of a compound of Formula (I) or a
form thereof further includes a use of the compound of Formula (Ia)
or a form thereof.
In one respect, for each of such embodiments, the subject is
treatment naive. In another respect, for each of such embodiments,
the subject is not treatment naive.
As used herein, the term "treating" refers to: (i) preventing a
disease, disorder or condition from occurring in a subject that may
be predisposed to the disease, disorder and/or condition but has
not yet been diagnosed as having it; (ii) inhibiting a disease,
disorder or condition, i.e., arresting its development; and/or
(iii) relieving a disease, disorder or condition, i.e., causing
regression of the disease, disorder and/or condition.
As used herein, the term "subject" refers to an animal or any
living organism having sensation and the power of voluntary
movement, and which requires for its existence oxygen and organic
food. Nonlimiting examples include members of the human, equine,
porcine, bovine, murine, canine and feline species. In some
embodiments, the subject is a mammal or a warm-blooded vertebrate
animal. In other embodiments, the subject is a human. As used
herein, the term "patient" may be used interchangeably with
"subject" and "human".
Another aspect of the invention relates to a method for treating a
viral infection by a wild type virus or a virus that is resistant
to a currently available antiviral agent, in a subject in need
thereof, comprising administering to the subject an effective
amount of a compound of Formula (I) or a form thereof.
Nonlimiting examples of viral infections intended to be included
within the scope of the invention include viral infections
resulting from viruses of the picornavirus genus (such as
poliovirus, hepatitis A virus, coxsackievirus and rhinovirus),
viruses of the coronaviridae genus (such as severe acute
respiratory syndrome (SARS)), viruses of the arbovirus genus,
viruses of the flavivirus genus (such as hepatitis C virus, yellow
fever, dengue and West Nile virus), herpesviruses (such as herpes
simplex virus and Kaposi's sarcoma-associated herpesvirus and other
viruses with a similar mode of replication), a human
immunodeficiency virus (HIV), or a human leukemia virus (HTLV).
As used herein, the terms "effective amount" or "therapeutically
effective amount" mean an amount of compound of Formula (I) or a
form, composition or medicament thereof effective in inhibiting the
above-noted diseases and thus producing the desired therapeutic,
ameliorative, inhibitory or preventative effect in a subject in
need thereof.
In general, the effective amount will be in a range of from about
0.001 mg/Kg/day to about 500 mg/Kg/day, or about 0.01 mg/Kg/day to
about 500 mg/Kg/day, or about 0.1 mg to about 500 mg/Kg/day, or
about 1.0 mg/day to about 500 mg/Kg/day, in single, divided, or a
continuous dose for a patient or subject having a weight in a range
of between about 40 to about 200 Kg (which dose may be adjusted for
patients or subjects above or below this range, particularly
children under 40 Kg). The typical adult subject is expected to
have a median weight in a range of between about 70 to about 100
Kg.
The dose administered to achieve an effective target plasma
concentration may also be administered based upon the weight of the
subject or patient. Doses administered on a weight basis may be in
the range of about 0.01 mg/kg/day to about 50 mg/kg/day, or about
0.015 mg/kg/day to about 20 mg/kg/day, or about 0.02 mg/kg/day to
about 10 mg/kg/day, or about 0.025 mg/kg/day to about 10 mg/kg/day,
or about 0.03 mg/kg/day to about 10 mg/kg/day, wherein said amount
is orally administered once (once in approximately a 24 hour
period), twice (once in approximately a 12 hour period) or thrice
(once in approximately an 8 hour period) daily according to subject
weight.
In another embodiment, where daily doses are adjusted based upon
the weight of the subject or patient, compounds of the invention
may be formulated for delivery at about 0.02, 0.025, 0.03, 0.05,
0.06, 0.075, 0.08, 0.09, 0.10, 0.20, 0.25, 0.30, 0.50, 0.60, 0.75,
0.80, 0.90, 1.0, 1.10, 1.20, 1.25, 1.50, 1.75, 2.0, 5.0, 10, 20 or
50 mg/kg/day. Daily doses adjusted based upon the weight of the
subject or patient may be administered as a single, divided, or
continuous dose. In embodiments where a dose of compound is given
more than once per day, it may be administered twice, thrice, or
more per day.
Within the scope of the present invention, the "effective amount"
of a compound of Formula (I) or a form thereof for use in the
manufacture of a medicament, the preparation of a pharmaceutical
kit or in a method for treating or ameliorating HCV infection or
disorders or symptoms associated therewith in a subject in need
thereof, is intended to include an amount in a range of from about
1.0 mg to about 3500 mg administered once daily; 10.0 mg to about
600 mg administered once daily; 0.5 mg to about 2000 mg
administered twice daily; or, an amount in a range of from about
5.0 mg to about 300 mg administered twice daily.
For example, the effective amount may be the amount required to
treat a HCV infection, or the amount required to inhibit viral
replication or infectivity, in a subject or, more specifically, in
a human. In some instances, the desired effect can be determined by
analyzing (1) the presence of HCV RNA; (2) the presence of anti-HCV
antibodies; (3) the level of serum alanine amino transferase (ALT)
and aspartate aminotransferase (AST) (ALT and AST are elevated in
patients chronically infected with HCV); (4) hepatocellular damage
resulting from HCV infection, including steatosis, fibrosis and
cirrhosis; (5) hepatocellular carcinoma as a result of chronic HCV
infection; and (6) extrahepatic sequelae (non-limiting examples
include pruritis, encephalopathies, mental disorders such as
anxiety or depression) of infection with HCV or other viruses. The
effective amount for a subject will depend upon various factors,
including the subject's body weight, size and health. Effective
amounts for a given patient can be determined by routine
experimentation that is within the skill and judgment of the
clinician.
For any compound, the effective amount can be estimated initially
either in cell culture assays or in relevant animal models, such as
a mouse, chimpanzee, marmoset or tamarin animal model. Relevant
animal models may also be used to determine the appropriate
concentration range and route of administration. Such information
can then be used to determine useful doses and routes for
administration in humans. Therapeutic efficacy and toxicity may be
determined by standard pharmaceutical procedures in cell cultures
or experimental animals, e.g., ED.sub.50 (the dose therapeutically
effective in 50% of the population) and LD.sub.50 (the dose lethal
to 50% of the population). The dose ratio between therapeutic and
toxic effects is the therapeutic index, and it can be expressed as
the ratio, LD.sub.50/ED.sub.50. In some embodiments, the effective
amount is such that a large therapeutic index is achieved. In
further embodiments, the dosage is within a range of circulating
concentrations that include an ED.sub.50 with little or no
toxicity. The dosage may vary within this range depending upon the
dosage form employed, sensitivity of the patient, and the route of
administration.
More specifically, the concentration-biological effect
relationships observed with regard to a compound of Formula (I) or
a form thereof indicate an trough target plasma concentration
ranging from approximately 0.001 .mu.g/mL to approximately 50
.mu.g/mL, from approximately 0.01 .mu.g/mL to approximately 20
.mu.g/mL, from approximately 0.05 .mu.g/mL to approximately 10
.mu.g/mL, or from approximately 0.1 .mu.g/mL to approximately 5
.mu.g/mL. To achieve such plasma concentrations, the compounds of
the invention may be administered at doses that vary from 0.1 .mu.g
to 100,000 mg, depending upon the route of administration in
single, divided, or continuous doses for a patient weighing between
about 40 to about 100 kg (which dose may be adjusted for patients
above or below this weight range, particularly children under 40
kg).
The exact dosage will be determined by the practitioner, in light
of factors related to the subject. Dosage and administration may be
adjusted to provide sufficient levels of the active agent(s) or to
maintain the desired effect. Factors which may be taken into
account include the severity of the disease state, general health
of the subject, ethinicity, age, weight, and gender of the subject,
diet, time and frequency of administration, drug combination(s),
reaction sensitivities, experience with other HCV therapies, and
tolerance/response to therapy. Long-acting pharmaceutical
compositions may be administered every 2, 3 or 4 days, once every
week, or once every two weeks depending on half-life and clearance
rate of the particular formulation.
The compounds and compositions of the present invention may be
administered to the subject via any drug delivery route known in
the art. Nonlimiting examples include oral, ocular, rectal, buccal,
topical, nasal, ophthalmic, subcutaneous, intramuscular,
intraveneous (bolus and infusion), intracerebral, transdermal, and
pulmonary routes of administration.
Metabolites of the Compounds of the Invention
Also falling within the scope of the present invention are the in
vivo metabolic products of the compounds described herein. Such
products may result, for example, from the oxidation, reduction,
hydrolysis, amidation, esterification and the like of the
administered compound, primarily due to enzymatic processes.
Accordingly, the invention includes compounds produced by a process
comprising contacting a compound of this invention with a mammalian
tissue or a mammal for a period of time sufficient to yield a
metabolic product thereof.
Such products typically are identified by preparing a radio-labeled
isotopologue (e.g. C.sup.14 or H.sup.3) of a compound of the
invention, administering the radio-labeled compound in a detectable
dose (e.g., greater than about 0.5 mg/kg) to a mammal such as a
rat, mouse, guinea pig, dog, monkey or human, allowing sufficient
time for metabolism to occur (typically about 30 seconds to about
30 hours), and identifying the metabolic conversion products from
urine, bile, blood or other biological samples. These products are
easily isolated since they are "radiolabeled" by virtue of being
isotopically-enriched (others are isolated by the use of antibodies
capable of binding epitopes surviving in the metabolite). The
metabolite structures are determined in conventional fashion, e.g.,
by MS or NMR analysis. In general, analysis of metabolites may be
done in the same way as conventional drug metabolism studies
well-known to those skilled in the art. The conversion products, so
long as they are not otherwise found in vivo, are useful in
diagnostic assays for therapeutic dosing of the compounds of the
invention even if they possess no biological activity of their
own.
Pharmaceutical Compositions
Embodiments of the present invention include the use of a compound
of Formula (I) or a form thereof in a pharmaceutical composition
for the prevention or treatment of a viral infection comprising an
effective amount of a compound of Formula (I) or a form thereof in
admixture with a pharmaceutically acceptable excipient.
As used herein, the term "composition" means a product comprising
the specified ingredients in the specified amounts, as well as any
product which results, directly or indirectly, from combination of
the specified ingredients in the specified amounts.
The pharmaceutical composition may be formulated to achieve a
physiologically compatible pH, ranging from about pH 3 to about pH
11. In some embodiments, the pharmaceutical composition is
formulated to achieve a pH of from about pH 3 to about pH 7. In
other embodiments, the pharmaceutical composition is formulated to
achieve a pH of from about pH 5 to about pH 8.
The term "pharmaceutically acceptable excipient" refers to an
excipient for administration of a pharmaceutical agent, such as the
compounds of the present invention. The term refers to any
pharmaceutical excipient that may be administered without undue
toxicity. Pharmaceutically acceptable excipients may be determined
in part by the particular composition being administered, as well
as by the particular mode of administration and/or dosage form.
Nonlimiting examples of pharmaceutically acceptable excipients
include carriers, solvents, stabilizers, adjuvants, diluents, etc.
Accordingly, there exists a wide variety of suitable formulations
of pharmaceutical compositions of the present invention (see, e.g.,
Remington's Pharmaceutical Sciences).
Suitable excipients may be carrier molecules that include large,
slowly metabolized macromolecules such as proteins,
polysaccharides, polylactic acids, polyglycolic acids, polymeric
amino acids, amino acid copolymers, and inactive virus particles.
Other exemplary excipients include antioxidants such as ascorbic
acid; chelating agents such as EDTA; carbohydrates such as dextrin,
hydroxyalkylcellulose, hydroxyalkylmethylcellulose, stearic acid;
liquids such as oils, water, saline, glycerol and ethanol; wetting
or emulsifying agents; pH buffering substances; and the like.
Liposomes are also included within the definition of
pharmaceutically acceptable excipients.
The pharmaceutical compositions of the invention may be formulated
in any form suitable for the intended method of administration.
Suitable formulations for oral administration include solids,
liquid solutions, emulsions and suspensions, while suitable
inhaleable formulations for pulmonary administration include
liquids and powders. Alternative formulations include syrups,
creams, ointments, tablets, and lyophilized solids which can be
reconstituted with a physiologically compatible solvent prior to
administration.
When intended for oral use for example, tablets, troches, lozenges,
aqueous or oil suspensions, non-aqueous solutions, dispersible
powders or granules (including micronized particles or
nanoparticles), emulsions, hard or soft capsules, syrups or elixirs
may be prepared. Compositions intended for oral use may be prepared
according to any method known to the art for the manufacture of
pharmaceutical compositions, and such compositions may contain one
or more agents including sweetening agents, flavoring agents,
coloring agents and preserving agents, in order to provide a
palatable preparation.
Pharmaceutically acceptable excipients suitable for use in
conjunction with tablets include, for example, inert diluents, such
as celluloses, calcium or sodium carbonate, lactose, calcium or
sodium phosphate; disintegrating agents, such as croscarmellose
sodium, cross-linked povidone, maize starch, or alginic acid;
binding agents, such as povidone, starch, gelatin or acacia; and
lubricating agents, such as magnesium stearate, stearic acid or
talc. Tablets may be uncoated or may be coated by known techniques
including microencapsulation to delay disintegration and adsorption
in the gastrointestinal tract and thereby provide a sustained
action over a longer period. For example, a time delay material
such as glyceryl monostearate or glyceryl distearate alone or with
a wax may be employed.
Formulations for oral use may be also presented as hard gelatin
capsules where the active ingredient is mixed with an inert solid
diluent, for example celluloses, lactose, calcium phosphate or
kaolin, or as soft gelatin capsules wherein the active ingredient
is mixed with non-aqueous or oil medium, such as glycerin,
propylene glycol, polyethylene glycol, peanut oil, liquid paraffin
or olive oil.
In other embodiments, pharmaceutical compositions of the invention
may be formulated as suspensions comprising a compound of Formula
(I) or a form thereof in admixture with at least one
pharmaceutically acceptable excipient suitable for the manufacture
of a suspension. In yet other embodiments, pharmaceutical
compositions of the invention may be formulated as dispersible
powders and granules suitable for preparation of a suspension by
the addition of one or more excipient(s).
Excipients suitable for use in connection with suspensions include
suspending agents, such as sodium carboxymethylcellulose,
methylcellulose, hydroxypropyl methylcelluose, sodium alginate,
polyvinylpyrrolidone, gum tragacanth, gum acacia, dispersing or
wetting agents such as a naturally occurring phosphatide (e.g.,
lecithin), a condensation product of an alkylene oxide with a fatty
acid (e.g., polyoxyethylene stearate), a condensation product of
ethylene oxide with a long chain aliphatic alcohol (e.g.,
heptadecaethyleneoxycethanol), a condensation product of ethylene
oxide with a partial ester derived from a fatty acid and a hexitol
anhydride (e.g., polyoxyethylene sorbitan monooleate); and
thickening agents, such as carbomer, beeswax, hard paraffin or
cetyl alcohol. The suspensions may also contain one or more
preservatives such as acetic acid, methyl and/or n-propyl
p-hydroxy-benzoate; one or more coloring agents; one or more
flavoring agents; and one or more sweetening agents such as sucrose
or saccharin.
The pharmaceutical compositions of the invention may also be in the
form of oil-in-water emulsions. The oily phase may be a vegetable
oil, such as olive oil or arachis oil, a mineral oil, such as
liquid paraffin, or a mixture of these. Suitable emulsifying agents
include naturally-occurring gums, such as gum acacia and gum
tragacanth; naturally occurring phosphatides, such as soybean
lecithin, esters or partial esters derived from fatty acids;
hexitol anhydrides, such as sorbitan monooleate; and condensation
products of these partial esters with ethylene oxide, such as
polyoxyethylene sorbitan monooleate. The emulsion may also contain
sweetening and flavoring agents. Syrups and elixirs may be
formulated with sweetening agents, such as glycerol, sorbitol or
sucrose. Such formulations may also contain a demulcent, a
preservative, a flavoring or a coloring agent.
Additionally, the pharmaceutical compositions of the invention may
be in the form of a sterile injectable preparation, such as a
sterile injectable aqueous emulsion or oleaginous suspension. Such
emulsion or suspension may be formulated according to the known art
using those suitable dispersing or wetting agents and suspending
agents which have been mentioned above. The sterile injectable
preparation may also be a sterile injectable solution or suspension
in a non-toxic parenterally acceptable diluent or solvent, such as
a solution in 1,2-propane-diol. The sterile injectable preparation
may also be prepared as a lyophilized powder. Among the acceptable
vehicles and solvents that may be employed are water, Ringer's
solution, and isotonic sodium chloride solution. In addition,
sterile fixed oils may be employed as a solvent or suspending
medium. For this purpose any bland fixed oil may be employed
including synthetic mono- or di-glycerides. In addition, fatty
acids such as oleic acid may likewise be used in the preparation of
injectables.
The compounds of the invention may be substantially insoluble in
water and sparingly soluble in most pharmaceutically acceptable
protic solvents and vegetable oils, but generally soluble in
medium-chain fatty acids (e.g., caprylic and capric acids) or
triglycerides and in propylene glycol esters of medium-chain fatty
acids. Thus, contemplated in the invention are compounds which have
been modified by substitutions or additions of chemical or
biochemical moieties which make them more suitable for delivery
(e.g., increase solubility, bioactivity, palatability, decrease
adverse reactions, etc.), for example by esterification,
glycosylation, PEGylation, etc.
In some embodiments, the compound of the invention is formulated
for oral administration in a lipid-based composition suitable for
low solubility compounds. Lipid-based formulations can generally
enhance the oral bioavailability of such compounds. As such,
pharmaceutical compositions of the invention may comprise a
effective amount of a compound of Formula (I) or a form thereof,
together with at least one pharmaceutically acceptable excipient
selected from medium chain fatty acids or propylene glycol esters
thereof (e.g., propylene glycol esters of edible fatty acids such
as caprylic and capric fatty acids) and pharmaceutically acceptable
surfactants, such as polyoxyl 40 hydrogenated castor oil.
In other embodiments, the bioavailability of low solubility
compounds may be enhanced using particle size optimization
techniques including the preparation of nanoparticles or
nanosuspensions using techniques known to those skilled in art. The
compound forms present in such preparations include amorphous,
partially amorphous, partially crystalline or crystalline
forms.
In alternative embodiments, the pharmaceutical composition may
further comprise one or more aqueous solubility enhancer(s), such
as a cyclodextrin. Nonlimiting examples of cyclodextrin include
hydroxypropyl, hydroxyethyl, glucosyl, maltosyl and maltotriosyl
derivatives of .alpha.-, .beta.-, and .gamma.-cyclodextrin, and
hydroxypropyl-.beta.-cyclodextrin (HPBC). In some embodiments, the
pharmaceutical composition further comprises HPBC in a range of
from about 0.1% to about 20%, from about 1% to about 15%, or from
about 2.5% to about 10%. The amount of solubility enhancer employed
may depend on the amount of the compound of the present invention
in the composition.
PREPARATION OF COMPOUNDS OF THE INVENTION
General Synthetic Examples
Methods for preparing certain compounds useful for treating or
ameliorating HCV infection or disorders or symptoms associated
therewith are available via standard, well-known synthetic
methodology and, furthermore, have been disclosed in U.S. patent
application Ser. No. 11/653,450 (referenced above), U.S. patent
application Ser. No. 11/653,448 (referenced above), U.S. patent
application Ser. No. 11/331,180 (referenced above) and U.S. patent
application Ser. No. 11/180,961 (referenced above), each of which
are incorporated herein by reference in their entirety and for all
purposes.
Similarly, as disclosed herein, methods for preparing the compounds
of the invention are available via standard, well-known synthetic
methodology. Many of the indole starting materials are commercially
available or can be prepared using the routes described below using
techniques known to those skilled in the art.
##STR00193##
Substituted indole Compound A1 can be substituted on the 3-position
with cyano using an appropriate cyanating agent Compound A2 (such
as chlorosulfonyl isocyanate or a dialkyl phosphoryl isocyanate and
the like) in a suitable solvent or solvent mixture (such as DMF,
CH.sub.3CN or dioxane and the like) to afford a Compound A3.
Compound A3 can then be reacted with a Compound A4 (wherein L
represents a leaving group and wherein Z is as previously defined)
to afford a Compound A5, representative of a compound of Formula
(I).
With respect to Compound A4, when the reactive functional group Z
includes, but is not limited to, C.sub.1-8alkyl and
aryl-C.sub.1-8alkyl and the L leaving group includes, but is not
limited to, a halide (such as chloro, bromo or iodo) or an
alkylsulfonate leaving group, the reaction can be carried out in a
suitable solvent in the presence of an inorganic base (such as
potassium carbonate or sodium hydride and the like) or an organic
base (such as a trialkylamine and the like).
With respect to Compound A4, when the reactive functional group Z
includes, but is not limited to, aryl or heteroaryl and the leaving
group L includes, but is not limited to, a halide leaving group
(such as chloro, bromo or iodo), the reaction can be carried out in
a polar or nonpolar solvent at a temperature of from about ambient
to about 200.degree. C. in the presence of a copper catalyst (such
as CuI and the like), and a base (such as Cs.sub.2CO.sub.3 or
K.sub.3PO.sub.4 and the like), and optionally with an amine ligand
(such as 1,2-bis(methylamino)ethane or 1,2-cyclohexanediamine and
the like).
Alternatively, Compound A1 can be reacted with Compound A4 to give
a Compound A6 that can then be reacted with Compound A2 as
described above to obtain Compound A5.
Additionally, iodination of Compound A6 provides Compound A7.
Subsequent reaction of Compound A7 with copper cyanide (CuCN) under
appropriate conditions provides Compound A5.
Reaction of the cyano group of Compound A5 under base conditions
(such as potassium hydroxide) affords Compound A8, the primary
amide, and further reaction affords Compound A9, the carboxylic
acid.
##STR00194##
Aldehyde substituted indole Compound B1 can be prepared by reacting
Compound A1 with a formylating reagent (such as phosphorous
oxychloride in the presence of DMF). Conversion of Compound B1 to
Compound B2, representative of a compound of Formula (I), can be
accomplished by treatment with Compound A4 as previously described
in Scheme A.
Alternatively, Compound A6 may be reacted with a formylating
reagent to directly provide Compound B2.
##STR00195##
Aldehyde substituted indole Compound B2 can be converted to the
oxime substituted indole Compound C1 via an aminating reagent (such
as hydroxylamine). Conversion of Compound C1 via dehydration, by
treatment with acetic anhydride and a base, or reaction with
thionyl chloride affords Compound A5, representative of a compound
of Formula (I).
##STR00196##
A nitroindole Compound D1 can be obtained by reacting Compound A1
with a nitrating agent (such as nitric acid or sodium nitrite and
the like) in a solvent (such as acetic acid, acetic anhydride or
sulfuric acid and the like or in a mixed solvent system further
containing an organic solvent such as dichloromethane and the
like). The reaction can be carried out a temperature of from about
-30.degree. C. to about 50.degree. C.
Compound D1 may be reacted with Compound A4 to provide Compound D2,
representative of a compound of Formula (I).
Alternatively, Compound A6 may be reacted in place of Compound A1
to directly provide Compound D2.
##STR00197##
Compound B2 may be reacted with a reagent (such as potassium
permanganate and the like) under aqueous conditions to provide
Compound E1, representative of a compound of Formula (I).
Further, Compound E1 may be reacted with thionyl chloride, followed
by reaction with a substituted amine (wherein the nitrogen atom may
be mono- or di-substituted with Ra, wherein Ra is C.sub.1-8alkyl)
to provide an amido substituted analog Compound E2, representative
of a compound of Formula (I).
##STR00198##
Substituted aniline Compound F1 can be diazotized and the resulting
diazonium salt reduced to give a phenyl hydrazine Compound F2.
Compound F2 is then reacted with ketone Compound F3 under acidic
conditions to provide Compound A1, which may be carried forward as
described in Scheme A to provide Compound A5, representative of a
compound of Formula (I).
The conditions for the cyclization reaction between Compound F2 and
Compound F3 can be carried out under typical conditions utilized by
one skilled in the art. For example, acidic conditions may be
provided using a Bronstead acid (such as acetic acid, hydrochloric
acid or polyphosphoric acid and the like) or a Lewis acid (such as
zinc chloride and the like). The reaction may be carried out in the
presence of a co-solvent (such as CH.sub.2Cl.sub.2 or THF and the
like), typically within a temperature range of from about 0.degree.
C. to about 120.degree. C.
##STR00199##
A Compound G1 can be converted to halogenated Compound G2 (wherein
Rb represents a halogen atom such as iodo or bromo) by reaction
with a strong base (such as n-butyllithium, s-butyllithium, lithium
diisopropylamide, lithium or potassium hexamethyldisilazide and the
like) in the presence of a suitable unreactive solvent (such as,
ether or THF) or in solvent mixtures containing such an unreactive
solvent to provide a 2-indolyl anion intermediate. The reaction is
typically carried out in the range of from about -78.degree. C. to
about ambient temperature. Generation of the intermediate can be
quenched with an electrophilic source of halogen (such as iodine,
bromine or N-bromosuccinimide and the like) to afford Compound
G2.
Compound G2 may then be reacted with a boronic acid in a Suzuki
reaction or with trialkyl stannane in a Stille reaction in the
presence of a palladium catalyst (such as
tetrakis(triphenylphosphine)palladium(0),
bis(triphenylphosphine)palladium(II) dichloride or palladium
acetate) and an added phosphine ligand, to afford a compound of
Formula (I).
The reaction is carried out in a suitable solvent (such as DMF,
toluene, dimethoxy ethane or dioxane and the like) at a temperature
of from about ambient to about 150.degree. C. For Suzuki
conditions, the reaction may be run with a base under aqueous
conditions (such as aqueous sodium carbonate or sodium bicarbonate
and the like) or under anhydrous conditions (such as with cesium or
potassium fluoride and the like). For Stille conditions, the
reaction may be run with a copper co-catalyst (such as copper
iodide and the like).
Alternatively, Compound G1 can be converted to a Compound G3
derivative (wherein Rc represents boronic acid or trialkylstannane)
by reacting the 2-indolyl anion intermediate described above with a
trialkylborate or halo-trialkyl stannane derivative (wherein halo
may be chloro, bromo or iodo), respectively. Compound G3 can then
be reacted with a Compound G4 (wherein L represents a halide
leaving group such as bromo or iodo), under either Suzuki or Stille
conditions to provide a compound of Formula (I).
A further method is to react Compound G1 under Heck conditions
(such as palladium acetate, silver (I) oxide, o-nitrobenzoic acid)
in a suitable solvent (such as DMF) with G4 to afford a compound of
Formula (I).
##STR00200##
A Compound H1 may be protected by reaction with a protecting group
(wherein PG.sub.1 represents a reactive protecting group such as
Boc anhydride and the like) to provide a Compound H2 (wherein PG
represents a protecting group such as Boc, benzyl, alkyl,
aryl-sulfonyl or trialkyl-silyl and the like). Treatment of
Compound H2 with a strong base (such as lithium diisopropyl amide
and the like) in an aprotic solvent (such as THF and the like),
followed by quenching with a trialkylborate derivative obtains a
Compound H3.
Reaction of Compound H3 with Compound G4 under reaction conditions
described in Scheme G provides Compound H4 and removal of the
protecting group affords Compound A1, which may be carried forward
as described in Scheme A to provide Compound A5, representative of
a compound of Formula (I).
##STR00201##
As described in Scheme H, Compound I1 can be used in place of
Compound H1 to provide a protected Compound I2.
As described in Scheme G, Compound I2 can be used in place of
Compound G1 to provide a halogenated Compound I3 (wherein Rd
represents a halogen atom such as iodo or bromo).
As described in Scheme H, Compound I3 can be used in place of
Compound H4 to provide a deprotected Compound I4.
As described in Scheme G, Compound I4 can be used in place of
Compound G2 in a Suzuki reaction with a boronic acid or ester in
the presence of a suitable palladium catalyst and an added
phosphine ligand, to afford a Compound I5.
As described in Scheme A, Compound I5 can be used in place of
Compound A1 to provide a compound of Formula (I).
##STR00202##
As described in Scheme G, Compound G1 is reacted to provide the
2-indolyl anion intermediate which can be quenched with a source of
zinc halide, (such as zinc halide metal or solutions thereof) to
give an organozinc compound Compound J1. Compound J1 can then be
reacted with a Compound J2 (wherein L represents leaving group such
as halogen or triflate and the like) in a Negishi reaction in the
presence of a suitable palladium catalyst to afford a compound of
Formula (I).
Alternatively, Compound G2 (wherein Rb is as described previously)
can be reacted with a Compound J3 in the presence of a suitable
palladium catalyst to provide a compound of Formula (I).
The conditions for the foregoing reactions include the presence of
a palladium catalyst (such as
tetrakis(triphenylphosphine)palladium(0) or
bis(triphenylphosphine)palladium(II)dichloride) in a suitable
solvent and a temperature in a range of from about ambient to about
150.degree. C.
Compound J3 may be prepared by treatment of an aryl halide with
activated zinc or by treatment of a lithium or magnesium
substituted R.sub.1--Ar compound with zinc halide.
##STR00203##
Compound K1 is iodinated under suitable conditions (such as
potassium iodide and potassium iodate or iodine monochloride) to
provide Compound K2. Compound K2 can then be reacted with a
Compound K3 in a Sonogashira reaction in the presence of a suitable
palladium catalyst (such as bis(triphenylphosphine)palladium
dichloride and the like) and copper co-catalyst (such as copper
iodide and the like) to afford Compound K4. Compound K4 is reacted
with either potassium tert-butoxide or a suitable copper catalyst
(such as copper iodide and the like) to provide Compound A6,
representative of a compound of Formula (I).
Alternatively, Compound K2 can be reacted with
trimethylsilylacetylene under Sonogashira conditions to give a
Compound K5. Removal of the trimethylsilyl group is accomplished
employing potassium hydroxide to afford Compound K6. Reaction of
Compound K6 with a compound L-Y (where L and Y has previously been
defined) under Sonogashira conditions provides Compound K4 which
can then be reacted as described above to obtain Compound A6,
representative of a compound of Formula (I).
##STR00204##
Reaction of Compound A7 with a vinyl iodide synthon with an
appropriate catalyst (such as palladium(II)acetate, dppp) and
subsequent treatment with aqueous acid affords Compound L1,
representative of a compound of Formula (I).
##STR00205##
Compound A6 can be reacted with a thiomethylating agent (such as
N-thiomethyl-phthalimide) in an appropriate solvent (such as
dimethyl acetamide) to provide Compound M1. Subsequent oxidation of
Compound M1 with an appropriate oxidant (such as mCPBA) and solvent
(such as chloroform) affords Compound M2, representative of a
compound of Formula (I).
##STR00206##
Compound H1 can be reacted with an acylating reagent (such as
trichloroacetylchloride and then KOH) to provide Compound O1.
Compound O1 may be reacted with Compound A4 to provide Compound O2.
Compound O2 can be converted to halogenated Compound O3 (wherein Rb
represents a halogen atom such as iodo or bromo) by reaction with a
strong base (such as n-butyllithium, s-butyllithium, lithium
diisopropylamide, lithium or potassium hexamethyldisilazide and the
like) in the presence of a suitable unreactive solvent (such as,
ether or THF) or in solvent mixtures containing such an unreactive
solvent to provide a 2-indolyl anion intermediate. The reaction is
typically carried out in the range of from about -78.degree. C. to
about ambient temperature. Generation of the intermediate can be
quenched with an electrophilic source of halogen (such as iodine,
bromine or N-bromosuccinimide and the like) to afford Compound
O3.
Compound O3 may then be reacted with a boronic acid in a Suzuki
reaction or with trialkyl stannane in a Stille reaction in the
presence of a palladium catalyst (such as
tetrakis(triphenylphosphine)palladium(0),
bis(triphenylphosphine)palladium(II)dichloride or palladium
acetate) and an added phosphine ligand, to afford a compound of
Compound O4, representative of a compound of Formula (I).
The reaction is carried out in a suitable solvent (such as DMF,
toluene, dimethoxy ethane or dioxane and the like) at a temperature
of from about ambient to about 150.degree. C. For Suzuki
conditions, the reaction may be run with a base under aqueous
conditions (such as aqueous sodium carbonate or sodium bicarbonate
and the like) or under anhydrous conditions (such as with cesium or
potassium fluoride and the like). For Stille conditions, the
reaction may be run with a copper co-catalyst (such as copper
iodide and the like).
Alternatively, Compound O2 can be converted to a Compound O5
derivative (wherein Rc represents boronic acid or trialkylstannane)
by reacting the 2-indolyl anion intermediate described above with a
trialkylborate or halo-trialkyl stannane derivative (wherein halo
may be chloro, bromo or iodo), respectively. Compound O5 can then
be reacted with a Compound G4 (wherein L represents a halide
leaving group such as bromo or iodo), under either Suzuki or Stille
conditions to provide a compound of Compound O4, representative of
a compound of Formula (I).
A further method is to react Compound O2 under Heck conditions
(such as palladium acetate, silver (I) oxide, o-nitrobenzoic acid)
to afford a compound of Compound O4, representative of a compound
of Formula (I).
Compound O4 can be reacted with KOH in a suitable solvent to
provide Compound E1 which can be reacted as in Scheme E to provide
E2, representative of a compound of Formula (I).
Specific Synthetic Examples
To assist in understanding the present invention, the following
Examples are included. The experiments relating to this invention
should not, of course, be construed as specifically limiting the
invention and such variations of the invention, now known or later
developed, which would be within the purview of one skilled in the
art are considered to fall within the scope of the invention as
described herein and hereinafter claimed.
Other than in the working examples, unless indicated to the
contrary, all numbers expressing quantities of ingredients,
reaction conditions, experimental data, and so forth used in the
specification and claims are to be understood as being modified by
the term "about". Accordingly, all such numbers represent
approximations that may vary depending upon the desired properties
sought to be obtained by a reaction or as a result of variable
experimental conditions. Therefore, within an expected range of
experimental reproducibility, the term "about" in the context of
the resulting data, refers to a range for data provided that may
vary according to a standard deviation from the mean. As well, for
experimental results provided, the resulting data may be rounded up
or down to present data consistently, without loss of significant
figures. At the very least, and not as an attempt to limit the
application of the doctrine of equivalents to the scope of the
claims, each numerical parameter should be construed in light of
the number of significant digits and ordinary rounding
techniques.
While the numerical ranges and parameters setting forth the broad
scope of the invention are approximations, the numerical values set
forth in the working examples are reported as precisely as
possible. Any numerical value, however, inherently contains certain
errors necessarily resulting from the standard deviation found in
their respective testing measurements.
Synthetic Examples
The present invention is described in more detail with reference to
the following non-limiting examples, which are offered to more
fully illustrate the invention, but are not to be construed as
limiting the scope thereof. The examples illustrate the preparation
of certain compounds of the invention, and the testing of these
compounds in vitro and/or in vivo. Those of skill in the art will
understand that the techniques described in these examples
represent techniques described by the inventors to function well in
the practice of the invention, and as such constitute preferred
modes for the practice thereof. However, it should be appreciated
that those of skill in the art should in light of the present
disclosure, appreciate that many changes can be made in the
specific methods that are disclosed and still obtain a like or
similar result without departing from the spirit and scope of the
invention.
As used above, and throughout the description of the invention, the
following abbreviations, unless otherwise indicated, shall be
understood to have the following meanings:
TABLE-US-00004 Abbreviation Meaning AcOH or HOAc acetic acid
.sup.tBu or tBu tert-butyl CSI chlorosulfonyl isocyanate DCM
dichloromethane (CH.sub.2Cl.sub.2) DIPA diisopropylamine DMF
dimethyl formamide DME dimethyl ether DMSO dimethylsulfoxide HPLC
high performance liquid chromatography iPR isopropyl KF potassium
fluoride LDA lithium diamine MeOH methanol MS mass spectroscopy
MTBE methyl tert-butyl ether NMR nuclear magnetic resonance
Pd.degree. palladium Pd.sub.2(dba).sub.3
tris(dibenzylideneacetone)dipalladium(0) PdCl.sub.2dppf
[1,1'-bis(diphenylphosphino)ferrocene] dichloropalladium(II)
Pd(PPh.sub.3).sub.4 tetrakis(triphenylphosphine)palladium
PHBF.sub.4 phosphonium tetrafluoroborate RT room temperature
Bu.sub.3SnI or ISnBu.sub.3 tributyltin iodide TFA trifluoroacetic
acid THF tetrahydrofuran TLC thin layer chromatography TMS
trimethylsilyl Tos tosyl
Example 1
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-(1,3-difluoropropan-
-2-yl)pyridine-3-sulfonamide (Cpd 35)
Step A. Preparation of 1,3-difluoro-2-propylamine hydrochloride
##STR00207##
1,3-difluoro-2-propanol (60.75 g, 633 mmol) was dissolved in
pyridine (375 mL) at 0.degree. C. Tosyl chloride (134 g, 700 mmol)
was added in portions and stirred overnight at room temperature.
Pyridine was removed under reduced pressure and the residue was
diluted with ethyl acetate. The mixture was washed sequentially
with dilute aqueous HCl, water, sat. aq. NaHCO.sub.3 and brine. The
organic layer was dried over MgSO.sub.4, filtered and concentrated.
The residue was cooled to -78.degree. C. until crystals began to
form. The material was triturated with ice-cold hexane (2.times.200
mL) and filtered to provide O-Tosyl-1,3-difluoro-2-propanol as a
white low-melting solid (143.9 g, 91%).
O-Tosyl-1,3-difluoro-2-propanol (30 g, 120 mmol), sodium azide (16
g, 246 mmol), and DMSO (60 mL) were combined and heated at
70.degree. C. for 5 h. The reaction mixture was then diluted in 500
mL of water and extracted with ethyl acetate (4.times.40 mL). The
organic layer was washed with 40 mL of water and brine. The mixture
was dried over MgSO.sub.4 and filtered into a 500 mL Parr bottle.
Pd/C (10%, 1.5 g) was added and the mixture shaken on a Parr
hydrogenator at 50 psi of H.sub.2 for 30 minutes. The bottle was
then quickly evacuated, charged again to 50 psi and shaken for
another 30 minutes. This process was repeated three more times. The
mixture was then filtered through celite and HCl (gas) was bubbled
through until completely saturated with HCl (30 minutes). Ethyl
acetate and HCl were evaporated to provide the title compound as a
white solid (12.3 g, 78%). .sup.1H NMR (DMSO-d.sub.6, 500 MHz):
.delta. 8.83 (3H, br s), 4.81 (1H, m), 4.72 (2H, m), 4.63 (1H, m),
3.78 (1H, m).
Part B. Preparation of
6-chloro-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide
##STR00208##
A solution of SO.sub.2 was prepared by adding thionyl chloride
(24.2 mL) into stirring water (144 mL) containing copper (I)
chloride (87.0 mg). The solution was then stirred at room
temperature overnight. 5-Amino-2-chloropyridine (10.0 g, 77.8 mmol)
was added into stirring conc. aq. HCl (80 mL) portionwise. The
mixture was stirred until all solid dissolved and was then cooled
to -5.degree. C. Into the mixture was added dropwise a solution of
sodium nitrite (5.9 g, 85.6 mmol) dissolved in 24 mL of water while
the temperature was kept between -5.degree. C. and 0.degree. C. The
resulting mixture was stirred for 30 minutes after the completion
of the addition and then added dropwise into the aqueous solution
of SO.sub.2. The temperature was kept below 0.degree. C. during the
addition. After the addition the mixture was stirred for 1 h below
0.degree. C. and then filtered. The cake was washed with ice-cold
water, dissolved in CH.sub.2Cl.sub.2, dried over Na.sub.2SO.sub.4
and concentrated to give 2-chloropyridine-5-sulfonyl chloride as a
grey solid (13.6 g, 82%). .sup.1H NMR (500 MHz, CDCl.sub.3):
.delta. 9.04 (1H, d, J=2.4 Hz), 8.27 (1H, dd, J=8.5 Hz, J=2.6 Hz),
7.62 (1H, dd, J=8.5 Hz, J=0.4 Hz).
2-Chloropyridine-5-sulfonyl chloride (18 g, 85 mmol) was added to a
solution of 1,3-difluoro-2-propylamine hydrochloride (11.2 g, 58.1
mmol) in pyridine (25 mL) at 0.degree. C. The reaction mixture was
stirred at room temperature for 30 minutes, diluted with ethyl
acetate (200 mL) and washed with 3N aq. HCl (3.times.100 mL). The
organic layer was dried over Na.sub.2SO.sub.4, filtered and
concentrated. The residue was triturated with hexane (2.times.50
mL) and filtered to provide the title compound as an off-white
solid (15.7 g, 70%). .sup.1H NMR (500 MHz, CDCl.sub.3): .delta.
8.79 (1H, d, J=2.4 Hz), 8.17 (1H, dd, J=2.6 Hz, 2.5 Hz), 7.49 (1H,
d, J=8.2 Hz), 5.25 (1H br s), 4.58 (2H, m), 4.47 (2H, m), 3.77 (1H,
m).
Part C. Preparation of
3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-ylboronic acid
##STR00209##
To 6-bromo-1H-indole (41.36 g, 211.0 mmol) in DMF (150 mL) at
-78.degree. C. was added chlorosulfonyl isocyanate (20 mL, 225
mmol). After complete addition, the mixture was allowed to warm to
room temperature and stirred for 2 hrs. The reaction mixture was
poured into ice (500 mL) and stirred for 30 minutes. The
precipitate was collected on a filter and dried in a vacuum oven to
give 6-bromo-1H-indole-3-carbonitrile as a light-beige solid (46.73
g, 100%).
To the 6-bromo-1H-indole-3-carbonitrile (20.28 g, 91.79 mmol) was
added cesium carbonate (76 g, 233 mmol), DMF (20 mL), and then
cyclobutylbromide
(96%, 11 mL, 112 mmol). This mixture was stirred overnight at
100.degree. C., cooled to room temperature and then poured into ice
water (500 mL). The precipitate was collected on a filter and
washed with ethyl ether (3.times.10 mL) and dried in a vacuum oven
at 50.degree. C. to give a first fraction of
6-bromo-1-cyclobutyl-1H-indole-3-carbonitrile as a light tan solid
(19.70 g). The ethyl ether wash was collected, concentrated and
triturated with ether to give a second fraction of
6-bromo-1-cyclobutyl-1H-indole-3-carbonitrile as a light orange
solid (2.90 g) (89% combined yield).
To 6-bromo-1-cyclobutyl-1H-indole-3-carbonitrile (1.13 g, 4.11
mmol) in a nitrogen flushed flask was added cyclopropylboronic acid
(0.62 g, 6.1 mmol), Pd.sub.2(dba).sub.3 (0.19 g, 0.21 mmol),
tri-tert-butylphosphonium tetrafluoroborate (0.14 g, 0.48 mmol),
potassium fluoride (1.43 g, 24.6 mmol). The dry reagents were
treated to three cycles of high vacuum/nitrogen backfill. Degassed
THF (16 mL) was added and the mixture was stirred overnight at
30.degree. C. THF was removed under a stream of nitrogen and then
CH.sub.2Cl.sub.2 (30 mL) was added. The mixture was stirred for 2
hours, filtered through celite, concentrated and chromatographed on
silica (0-10% ethyl acetate 1:1 in CH.sub.2Cl.sub.2/hexanes) to
give 0.68 g of white solid containing ca. 1%
3-cyano-1-N-cyclobutylindole. The impurity was removed via a hot
hexane wash; the solid was heated to 70.degree. C. in hexane and
then filtered (combined material, 11.2 g, gave 9.1 g of pure
material) to provide
1-cyclobutyl-6-cyclopropyl-1H-indole-3-carbonitrile. .sup.1H NMR
(500 MHz, acetone-d.sub.6): .delta. 8.15 (1H, s), 7.54 (1H, d,
J=7.9 Hz), 7.35 (1H, s), 7.06 (1H, dd, J=8.2 Hz, J=1.4 Hz), 5.09
(1H, p, J=8.0 Hz), 2.72-2.61 (2H, m), 2.59-2.48 (2H, m), 2.12-2.05
(2H, m), 2.03-1.93 (3H, m), 1.00 (2H, ddd, J=8.4 Hz, J=6.4 Hz,
J=4.4 Hz), 0.80-0.74 (2H, m).
Into a solution of
1-cyclobutyl-6-cyclopropyl-1H-indole-3-carbonitrile (2.0 g, 8.47
mmol) and triisopropyl borate (3.52 mL, 15.25 mmol) in THF (35 mL)
at -78.degree. C. was added LDA (1.5 M in cyclohexane, 7.3 mL,
11.01 mmol). The mixture was stirred at -78.degree. C. for 30 min,
quenched with ice water (60 mL) and stirred for 15 min without
cooling. The mixture was extracted with ethyl acetate 1:1 in hexane
(20 mL). The aqueous layer was acidified with 2 N aq. HCl to pH 5
and then extracted with CH.sub.2Cl.sub.2 (60 mL). The organic layer
was dried over Na.sub.2SO.sub.4 and concentrated to give the title
compound as a solid (2.5 g, 70% pure by LCMS) that was used in the
next step without further purification.
Part D. Preparation of
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N-(1,3-difluoropropa-
n-2-yl)pyridine-3-sulfonamide
##STR00210##
A mixture of
3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-ylboronic acid (0.46
g, 1.15 mmol),
6-chloro-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide (0.17 g,
0.63 mmol), tri-tert-butylphosphonium tetrafluoroborate (20 mg,
0.069 mmol), Pd.sub.2(dba).sub.3 (32 mg, 0.035 mmol) and potassium
fluoride (0.4 g, 6.9 mmol) in THF (4.0 mL) was stirred at
40.degree. C. overnight. The solvent was then evaporated and the
residue purified by flash chromatography with 0-10% ethyl acetate
in CH.sub.2Cl.sub.2 to provide the title Compound 35 (220 mg, 74%).
Melting point: 175-178; MS m/z 471.1 M+H.sup.+; .sup.1H NMR (500
MHz, CDCl.sub.3): .delta. 9.23 (1H, s), 8.33 (1H, dd, J=8.2 Hz,
J=2.2 Hz), 8.01 (1H, d, J=8.2 Hz), 7.68 (1H, d, J=8.3 Hz), 7.45
(1H, s), 7.05 (1H, t, J=7.0 Hz), 5.36-5.31 (1H, m), 5.23 (1H, d,
J=8.4 Hz), 4.63-4.44 (4H, m), 3.98-3.83 (1H, m), 2.69-2.60 (2H, m),
2.50-2.40 (2H, m), 2.14-2.08 (1H, m), 2.00-1.82 (2H, m), 1.12-1.05
(2H, m), 0.82-0.77 (2H, m).
Additional compounds representative of the present invention may be
prepared according to the procedure of Example 1 by substituting
the appropriate starting materials, reagents and reaction
conditions and include compounds selected from (wherein MS
represents mass spec as MH.sup.+, unless otherwise indicated, m.p.
represents melting point in .degree. C., and N/A indicates that the
data was not obtained):
TABLE-US-00005 Cpd Name m.p. MS 5
6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N- 203-205 413.2
(propan-2-yl)pyridine-3-sulfonamide 6
6-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]- 160-162
413.2 N-(propan-2-yl)pyridine-3-sulfonamide 7
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N- 174-176
435.3 (propan-2-yl)pyridine-3-sulfonamide 8
6-(3-cyano-1-cyclobutyl-5-cyclopropyl-1H-indol-2-yl)-N- 172-174
435.2 (propan-2-yl)pyridine-3-sulfonamide 9
N-tert-butyl-6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2- 181-185
427.1 yl)pyridine-3-sulfonamide 14
6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N- N/A 429.3
(propan-2-yl)pyridine-3-sulfonamide 15
N-tert-butyl-6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2- 195-197
443.2- yl)pyridine-3-sulfonamide 27
5-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N- N/A 435.3
(propan-2-yl)pyridine-2-sulfonamide 28
5-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N- N/A 429.2
(propan-2-yl)pyridine-2-sulfonamide 29
6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-(1,3- 206-208
449.0 difluoropropan-2-yl)pyridine-3-sulfonamide 30
6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(1,3- 182-186
465.0 difluoropropan-2-yl)pyridine-3-sulfonamide 37
6-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(1,3- 200-202
465.0 difluoropropan-2-yl)pyridine-3-sulfonamide 38
6-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-(1,3- 171-172
463.3 difluoropropan-2-yl)pyridine-3-sulfonamide 46
6-[3-cyano-5-fluoro-1-(tetrahydrofuran-3-yl)-1H-indol-2- 194-197
465.1 yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 47
6-[3-cyano-5-fluoro-1-(tetrahydrofuran-3-yl)-1H-indol-2- 185-188
429.0 yl]-N-(propan-2-yl)pyridine-3-sulfonamide 56
6-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-(1,3- 206-208
448.5 difluoropropan-2-yl)pyridine-3-sulfonamide 57
6-[3-cyano-1-(cyclopropylmethyl)-6-fluoro-1H-indol-2-yl]- 188-190
449.0- N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 58
6-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]- 162-164
448.5- N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 60
6-[3-cyano-5-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3- 168-170
437.- 0 difluoropropan-2-yl)pyridine-3-sulfonamide 61
6-[3-cyano-6-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3- 155-156
437.- 3 difluoropropan-2-yl)pyridine-3-sulfonamide 62
6-[6-chloro-3-cyano-1-(cyclopropylmethyl)-1H-indol-2-yl]- 223-227
464.9- N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 63
6-[6-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N- 200-202 453.0
(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 64
6-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3- 236-240
479.0 difluoropropan-2-yl)pyridine-3-sulfonamide 65
6-[5-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N- 212-215 452.8
(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 66
6-(3-cyano-1-cyclopentyl-7-fluoro-1H-indol-2-yl)-N- 152-153 427.0
(propan-2-yl)pyridine-3-sulfonamide 71
2-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N- 192-193
436.5 (propan-2-yl)pyrimidine-5-sulfonamide 72
6-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3- N/A 479.0
difluoropropan-2-yl)pyridine-3-sulfonamide 73
6-[5-chloro-3-cyano-1-(cyclopropylmethyl)-1H-indol-2-yl]- N/A 464.9
N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 79
6-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-(1,3- N/A 493.9
difluoropropan-2-yl)pyridine-3-sulfonamide 83
6-[3-cyano-6-cyclopropyl-1-(propan-2-yl)-1H-indol-2-yl]- 184-190
459.1 N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 84
6-[3-cyano-6-cyclopropyl-1-(cyclopropylmethyl)-1H- N/A 471.0
indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3- sulfonamide 85
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N- 194-200
485.0 (1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 86
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N- 166-170
503.5 (1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide 87
6-(3-cyano-1-cyclopentyl-7-fluoro-1H-indol-2-yl)-N-(1,3- 128-129
462.9 difluoropropan-2-yl)pyridine-3-sulfonamide 88
6-(7-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3- 149-150
410.8 difluoropropan-2-yl)pyridine-3-sulfonamide 89
6-(6-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-(1,3- 203-207
492.9 difluoropropan-2-yl)pyridine-3-sulfonamide 90
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2- N/A 393.0
yl)pyridine-3-sulfonamide 92
6-(3-cyano-1-cyclohexyl-6-cyclopropyl-1H-indol-2-yl)-N- 193-198
499.0 (1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 97
2-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N- 210-215 458.0
(propan-2-yl)pyrimidine-5-sulfonamide 104
6-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-(1,3- 138-141
477.0 difluoropropan-2-yl)pyridine-3-sulfonamide 109
6-(3-cyano-1,6-dicyclopropyl-1H-indol-2-yl)-N-(propan-2- 209-208
421.4- yl)pyridine-3-sulfonamide 114
2-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N- >198.0 430.0
(propan-2-yl)pyrimidine-5-sulfonamide decomp. 115
2-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N- 228-229 430.0
(propan-2-yl)pyrimidine-5-sulfonamide 120
2-[5-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N- 202-220 418.6
(propan-2-yl)pyrimidine-5-sulfonamide 123
2-[3-cyano-5-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N- 192-197 402.0
(propan-2-yl)pyrimidine-5-sulfonamide 124
2-[3-cyano-6-cyclopropyl-1-(cyclopropylmethyl)-1H- 169-174 436.0
indol-2-yl]-N-(propan-2-yl)pyrimidine-5-sulfonamide 125
2-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N- 211-212
450.0- (propan-2-yl)pyrimidine-5-sulfonamide 126
2-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N- 165-168
472.0 (1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 138
2-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N- 193-195 414.0
(propan-2-yl)pyrimidine-5-sulfonamide 139
2-[3-cyano-1-(cyclopropylmethyl)-6-fluoro-1H-indol-2-yl]- 218-219
414.- 6 N-(propan-2-yl)pyrimidine-5-sulfonamide 140
2-[3-cyano-6-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N- 158-160 402.6
(propan-2-yl)pyrimidine-5-sulfonamide 141
2-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N- 216-217 428.1
(propan-2-yl)pyrimidine-5-sulfonamide 147
6-(3-cyano-1,6-dicyclopropyl-1H-indol-2-yl)-N-(1,3- 226-228 457.7
difluoropropan-2-yl)pyridine-3-sulfonamide 148
2-(3-cyano-1,6-dicyclopropyl-1H-indol-2-yl)-N-(1,3- 259-260 422.7
difluoropropan-2-yl)pyrimidine-5-sulfonamide 153
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N- 166-171
501.0 [1-(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide 156
2-[6-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N- N/A 418.0
(propan-2-yl)pyrimidine-5-sulfonamide 157
2-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3- 233-238
479.9- difluoropropan-2-yl)pyrimidine-5-sulfonamide 163
2-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-(1,3- 193-195
449.9 difluoropropan-2-yl)pyrimidine-5-sulfonamide 164
2-[3-cyano-1-(cyclopropylmethyl)-6-fluoro-1H-indol-2-yl]- 176-178
449.- 9 N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 165
2-[3-cyano-6-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N-(1,3- 149-150
438- .1 difluoropropan-2-yl)pyrimidine-5-sulfonamide 166
2-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-(1,3- 167-169
464.0- difluoropropan-2-yl)pyrimidine-5-sulfonamide 173
2-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N- 215-219
486.1- (1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 175
2-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(1,3- 210-212
465.9 difluoropropan-2-yl)pyrimidine-5-sulfonamide 176
2-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(1,3- 243-246
465.8 difluoropropan-2-yl)pyrimidine-5-sulfonamide 187
2-[5-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N- N/A 453.9
(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 188
2-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3- N/A 479.9
difluoropropan-2-yl)pyrimidine-5-sulfonamide 189
2-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N- N/A 443.9
(propan-2-yl)pyrimidine-5-sulfonamide 193
2-(3-cyano-1-cyclohexyl-6-cyclopropyl-1H-indol-2-yl)-N- >200
500.0 (1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide decomp. 221
2-[5-chloro-3-cyano-1-(cyclopropylmethyl)-1H-indol-2-yl]- 245-250
465.- 9 N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 234
6-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-(1,3- 193-199
477.1 difluoropropan-2-yl)pyridine-3-sulfonamide 235
2-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-(1,3- 213-218
478.1 difluoropropan-2-yl)pyrimidine-5-sulfonamide 240
2-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-(1,3- 201-206
464.0- difluoropropan-2-yl)pyrimidine-5-sulfonamide 243
6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(3,3- N/A 477.0
difluorocyclobutyl)pyridine-3-sulfonamide 244
6-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-(3,3- 135-138
477.1 difluorocyclobutyl)pyridine-3-sulfonamide 247
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N- 176-178
483.2 (3,3-difluorocyclobutyl)pyridine-3-sulfonamide 251
2-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N- 200-202 442.1
(propan-2-yl)pyrimidine-5-sulfonamide 257
2-[6-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N- N/A 454.1
(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 264
2-(3-cyano-1,6-dicyclobutyl-1H-indol-2-yl)-N-(1,3- 184-188 486.0
difluoropropan-2-yl)pyrimidine-5-sulfonamide 265
2-(3-cyano-1,6-dicyclobutyl-1H-indol-2-yl)-N-(propan-2- 192-194
450.0 yl)pyrimidine-5-sulfonamide 266
6-(3-cyano-1,6-dicyclobutyl-1H-indol-2-yl)-N-(propan-2- 178-180
449.0 yl)pyridine-3-sulfonamide 287
N-[5-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2- 239-241 407.1
yl)pyridin-2-yl]methanesulfonamide 288
N-[5-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2- 241-243 421.3
yl)pyridin-2-yl]ethanesulfonamide 289
N-[5-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2- 226-228 435.3
yl)pyridin-2-yl]propane-2-sulfonamide 298
N-[6-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2- 230-235 455.3
yl)pyridin-3-yl]cyclopropanesulfonamide 302
2-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]- 216-221
450.- 2 N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 303
2-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]- 215-220
414.- 3 N-(propan-2-yl)pyrimidine-5-sulfonamide 306
2-[3-cyano-1-cyclohexyl-6-(trifluoromethoxy)-1H-indol-2- 168-170
544.1- yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 307
6-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-(1,3- 166-168
463.0- difluoropropan-2-yl)pyridine-3-sulfonamide 308
6-[3-cyano-1-(propan-2-yl)-6-(trifluoromethoxy)-1H-indol- 144-145
493.- 2 2-yl]-N-[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 309
6-[3-cyano-1-(cyclopropylmethyl)-6-(trifluoromethoxy)- 115-117
505.2 1H-indol-2-yl]-N-[(1S)-1-cyclopropylethyl]pyridine-3-
sulfonamide 310
6-(3-cyano-1-cyclopentyl-6-ethyl-1H-indol-2-yl)-N-(1,3- 204.5-205.0
47- 3.1 difluoropropan-2-yl)pyridine-3-sulfonamide 311
6-(3-cyano-1-cyclopentyl-6-ethyl-1H-indol-2-yl)-N-[(2R)- 185-186
491.2- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 312
6-(3-cyano-1-cyclopentyl-6-ethyl-1H-indol-2-yl)-N-[(1S)-
147.5-148.5 4- 63.2 1-cyclopropylethyl]pyridine-3-sulfonamide 314
2-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N- 239-245 444.0
(propan-2-yl)pyrimidine-5-sulfonamide 315
2-[3-cyano-1-cyclobutyl-6-(fluoromethyl)-1H-indol-2-yl]- N/A 428.0
N-(propan-2-yl)pyrimidine-5-sulfonamide 316
6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(2R)- N/A 482.9
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 317
6-[3-cyano-1-cyclobutyl-6-(fluoromethyl)-1H-indol-2-yl]- N/A 453.0
N-[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 318
6-[3-cyano-1-cyclobutyl-6-(fluoromethyl)-1H-indol-2-yl]- N/A 463.0
N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 319
6-[3-cyano-1-cyclobutyl-6-(fluoromethyl)-1H-indol-2-yl]- 200-213
480.9- N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
320 6-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol- 133-134
519.0 2-yl]-N-[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 321
2-[3-cyano-1-cyclobutyl-6-(morpholin-4-yl)-1H-indol-2- 223-225
517.3 yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 322
6-[3-cyano-1-cyclobutyl-6-(morpholin-4-yl)-1H-indol-2- 241-242
516.3 yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 324
2-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N- 214-215
490.2 [(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 325
2-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(2S)- 242-243
464.2- 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 330
2-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]- N/A
482.0 N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 331
6-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]- 217-222
481- .0 N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 332
2-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]- 221-227
446- .0 N-(propan-2-yl)pyrimidine-5-sulfonamide 333
6-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]- 212-220
445- .1
N-(propan-2-yl)pyridine-3-sulfonamide 334
6-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]- 200-206
499- .0 N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
335 6-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]-
182-189 471- .1 N-[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide
338 6-(3-cyano-1-cyclobutyl-6-ethyl-1H-indol-2-yl)-N-[(2S)- 198-199
477.2 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 339
6-(3-cyano-1-cyclobutyl-5-ethyl-1H-indol-2-yl)-N-[(2S)- 168-169
477.2 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 342
6-(3-cyano-1,6-dicyclobutyl-1H-indol-2-yl)-N-(1,3- Foam 485.3
difluoropropan-2-yl)pyridine-3-sulfonamide 343
6-(3-cyano-6-cyclobutyl-1-cyclopentyl-1H-indol-2-yl)-N- 176-178
517.3 [(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 344
2-[3-cyano-6-cyclopropyl-1-(cyclopropylmethyl)-1H- 205-210 472.2
indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5- sulfonamide
345 6-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N- 195-200
477.2 [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 346
6-(3,5-dicyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)- 225-228 488.3
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 347
6-[3,6-dicyano-1-(cyclopropylmethyl)-1H-indol-2-yl]-N- 199-201
456.1 (1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 348
6-[3,6-dicyano-1-(cyclopropylmethyl)-1H-indol-2-yl]-N- 190-192
420.2 (propan-2-yl)pyridine-3-sulfonamide 349
6-[3,6-dicyano-1-(cyclopropylmethyl)-1H-indol-2-yl]-N- 187-188
474.2 [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 350
N-[(1S)-1-cyclopropylethyl]-6-[3,6-dicyano-1- 203-208 463.2
(cyclopropylmethyl)-1H-indol-2-yl]pyridine-3-sulfonamide 358
6-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol- 168-170
546.9 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 360
6-(6-chloro-3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)- 203-206
501.- 0 N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
361 2-[3-cyano-1-cyclobutyl-6-(fluoromethyl)-1H-indol-2-yl]-
226-232 464.4- N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide
362 6-[3-cyano-1-cyclobutyl-6-(fluoromethyl)-1H-indol-2-yl]-
205-209 481.3-
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 363
6-[3-cyano-1-cyclobutyl-6-(difluoromethyl)-1H-indol-2-yl]- 198-207
499- .2 N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
364 6-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)- N/A
497.2 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 365
6-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)- 207-214
497.- 3 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 367
N-[(1S)-1-cyclopropylethyl]-2-(3,5-dicyano-1-cyclopentyl- 218-223
461.- 2 1H-indol-2-yl)pyrimidine-5-sulfonamide 372
6-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2- 175-180 463.3
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide 373
6-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2- 186-188 445.3
yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 374
6-(3-cyano-1-cyclopentyl-5-ethyl-1H-indol-2-yl)-N-[(2S)-
159.5-160.5 4- 91.1
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 375
6-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(2S)- 198-204
482.9- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 376
6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(2S)- 193-198
483.2- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 377
2-[3-cyano-1-cyclobutyl-5-(fluoromethyl)-1H-indol-2-yl]- 131-134
464.0- N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 378
6-[3-cyano-1-cyclobutyl-5-(difluoromethyl)-1H-indol-2-yl]- N/A
481.1 N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 379
2-[3-cyano-1-cyclobutyl-5-(difluoromethyl)-1H-indol-2-yl]- N/A
482.1 N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 380
2-[3-cyano-1-cyclobutyl-5-(difluoromethyl)-1H-indol-2-yl]- 186-188
500- .1 N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-
sulfonamide 381
6-(3-cyano-1-cyclopentyl-5-ethyl-1H-indol-2-yl)-N-(1,3- 167-168
473.1 difluoropropan-2-yl)pyridine-3-sulfonamide 384
6-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-1H-indol-2- 172-174
513.- 0 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 385
2-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-1H-indol-2- 216-218
514.- 1 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-
sulfonamide 388
2-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2- 219-222 410.2
yl]-N-(propan-2-yl)pyrimidine-5-sulfonamide 389
2-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2- 220-223 464.1
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5- sulfonamide
390 2-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-[(2S)-
218-223 492.2- 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide
391 2-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N- 180-185
478.2 [(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 392
2-(3,5-dicyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)- 250-254 489.4
1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 393
2-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-[(2S)- 236-238
496.1- 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 394
6-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-[(2S)- 213-215
495.1- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 395
6-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-[(2S)- 171-172
467.2- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 396
6-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-[(2S)- 132-133
481.- 1 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 397
6-[3-cyano-1-(cyclopropylmethyl)-6-fluoro-1H-indol-2-yl]- 174-175
467.- 1 N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
401 2-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N-
238-239 504.3-
[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 402
2-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2- 259-260 464.2
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5- sulfonamide
403 2-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N- 235-236
452.3 [(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 404
2-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N- 223-224 478.3
[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 405
2-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N- 254-255 480.3
[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 406
2-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N- 211-212 494.3
[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 410
6-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-[(2S)- 209-211
495.2- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 411
2-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-[(2S)- 224-226
496.3- 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 412
6-[3-cyano-1-(cyclohex-2-en-1-yl)-5-fluoro-1H-indol-2-yl]- 187-188
493- .1 N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
413 6-[3-cyano-1-(cyclohex-2-en-1-yl)-5-fluoro-1H-indol-2-yl]-
186-187 493- .0
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 414
2-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[(2S)- 190-195
464.3- 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 415
2-[6-chloro-3-cyano-1-(cyclopropylmethyl)-1H-indol-2-yl]- N/A 483.9
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5- sulfonamide 416
2-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N- 195-200 414.2
(propan-2-yl)pyrimidine-5-sulfonamide 417
2-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)- 220-224
497.- 8 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 418
2-[6-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N- 241-248 471.9
[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 419
2-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)- 243-249
497.- 8 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 420
2-[5-chloro-3-cyano-1-(propan-2-yl)-1H-indol-2-yl]-N- N/A 471.8
[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 425
6-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N- N/A 422.9
[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 426
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N- N/A 449.0
[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 427
6-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N- 206-212 478.9
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 428
6-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N- 206-212 478.9
[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 429
6-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N- 193-199 450.9
[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 430
6-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N- 209-216 492.9
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 431
6-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N- 209-216 492.9
[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 432
6-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N- 199-209 465.0
[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 433
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)-N- N/A 475.0
[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 434
6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[(2S)- N/A 466.8
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 435
6-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-[(2S)- N/A 481.3
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 436
6-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]- 165-167
467.- 2 N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
444 6-(5-chloro-3-cyano-1-cyclobutyl-6-methyl-1H-indol-2- 189-193
478.9 yl)-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 445
6-(5-chloro-3-cyano-1-cyclobutyl-6-methyl-1H-indol-2- 213-215 497.4
yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide 446
6-(5-chloro-3-cyano-1-cyclobutyl-6-methyl-1H-indol-2- 209-210 496.8
yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide 447
2-(5-chloro-3-cyano-1-cyclobutyl-6-methyl-1H-indol-2- 275-279 480.3
yl)-N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 448
2-(5-chloro-3-cyano-1-cyclobutyl-6-methyl-1H-indol-2- >300 498.2
yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5- sulfonamide
451 2-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[(2S)-
198-203 468.3- 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide
452 2-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-(1,3- 175-180
450.4 difluoropropan-2-yl)pyrimidine-5-sulfonamide 453
6-(3-cyano-1-cyclobutyl-5-methoxy-1H-indol-2-yl)-N- 181-183 479.4
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 454
2-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(2S)- 232-234
483.9- 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 455
2-[3-cyano-1-cyclobutyl-6-(propan-2-yl)-1H-indol-2-yl]-N- 217-222
492.- 0 [(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide
456 6-[3-cyano-1,6-di(propan-2-yl)-1H-indol-2-yl]-N-(1,3- 165-173
461.0 difluoropropan-2-yl)pyridine-3-sulfonamide 457
6-[3-cyano-1-cyclopentyl-6-(propan-2-yl)-1H-indol-2-yl]- 163-172
487.0- N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 458
6-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2- 166-172 463.0
yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide 459
6-[3-cyano-1-cyclohexyl-6-(trifluoromethoxy)-1H-indol-2- N/A 561.2
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide 460
6-[3-cyano-1-(cyclopropylmethyl)-6-(propan-2-yl)-1H- 132-134 473.4
indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3- sulfonamide 461
6-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-[(2R)- 226-227
511.2- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 462
6-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-[(2S)- 220-222
511.3- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 463
2-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-(1,3- 251-253
494.2 difluoropropan-2-yl)pyrimidine-5-sulfonamide 464
2-(5-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-[(2S)- 253-255
512.2- 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 465
6-(3,6-dicyano-1-cyclobutyl-1H-indol-2-yl)-N-(1,3- 203-204 455.9
difluoropropan-2-yl)pyridine-3-sulfonamide 466
2-(3,6-dicyano-1-cyclobutyl-1H-indol-2-yl)-N-(1,3- 240-241 456.9
difluoropropan-2-yl)pyrimidine-5-sulfonamide 467
6-(3,6-dicyano-1-cyclobutyl-1H-indol-2-yl)-N-[(2S)-1,1,1- 223-225
474.- 0 trifluoropropan-2-yl]pyridine-3-sulfonamide 468
6-(3,6-dicyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3- 219-221 470.0
difluoropropan-2-yl)pyridine-3-sulfonamide 469
2-(3,6-dicyano-1-cyclopentyl-1H-indol-2-yl)-N-(1,3- 246-247 471.0
difluoropropan-2-yl)pyrimidine-5-sulfonamide 470
6-(3,6-dicyano-1-cyclopentyl-1H-indol-2-yl)-N-[(2S)- 203-205 488.0
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 478
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N- 222-227 477.4
(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3- sulfonamide
479 6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2- 165-171
529.2 yl]-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-
sulfonamide 480 6-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-
182-187 477.0 (1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-
sulfonamide 484
6-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[(2R)- 134-142
463.0- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 485
6-[3-cyano-5-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N- 167-173 451.0
[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 486
6-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N- N/A 477.0
[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 487
6-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-[(2R)- 180-189
491.0- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 494
2-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-[(2S)- 223-225
468.3- 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 495
2-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-[(2S)- 217-219
482.- 4 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 496
2-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-[(1S)- 207-208
440.2- 1-cyclopropylethyl]pyrimidine-5-sulfonamide 497
2-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N-[(1S)- N/A 454.3
1-cyclopropylethyl]pyrimidine-5-sulfonamide 498
2-[3-cyano-1-(cyclopropylmethyl)-6-fluoro-1H-indol-2-yl]- 198-199
440.- 2 N-[(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide 499
2-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-[(1S)- 169-170
468.3- 1-cyclopropylethyl]pyrimidine-5-sulfonamide 500
6-(3-cyano-1-cyclobutyl-5-methoxy-1H-indol-2-yl)-N- 181-186 479.3
[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 505
6-(6-chloro-3-cyano-1-cyclobutyl-5-methyl-1H-indol-2- 195-196 479.2
yl)-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 506
6-(6-chloro-3-cyano-1-cyclobutyl-5-methyl-1H-indol-2- 198-198.5
479.2 yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 507
2-(6-chloro-3-cyano-1-cyclobutyl-5-methyl-1H-indol-2- 217-218 444.1
yl)-N-(propan-2-yl)pyrimidine-5-sulfonamide 510
6-(6-chloro-3-cyano-1-cyclobutyl-5-methyl-1H-indol-2- 200-200.5
497.2 yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 511 6-(1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(1,3-
137-139 420.2 difluoropropan-2-yl)pyridine-3-sulfonamide 513
6-(3-cyano-1-cyclohexyl-6-methyl-1H-indol-2-yl)-N-(1,3- 195-203
473.3 difluoropropan-2-yl)pyridine-3-sulfonamide 514
6-(6-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-[(2R)- 218-223
511.2- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 515
6-(6-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-[(2S)- 217-224
511.2- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 516
2-(6-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-[(2S)- 215-220
512.2- 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 517
2-(6-chloro-3-cyano-1-cyclohexyl-1H-indol-2-yl)-N-(1,3- 228-234
494.2 difluoropropan-2-yl)pyrimidine-5-sulfonamide 518
6-(3-cyano-1-cyclohexyl-6-methoxy-1H-indol-2-yl)-N- 198-204 507.2
[(2R)-1,1,1-trifluoropropan-2-yl]-pyridine-3-sulfonamide 519
6-(3-cyano-1-cyclohexyl-6-methoxy-1H-indol-2-yl)-N- 197-204 507.2
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 520
2-(3-cyano-1-cyclohexyl-6-methoxy-1H-indol-2-yl)-N- 209-215 490.2
(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 521
6-(6-chloro-3-cyano-1-cyclopentyl-5-methyl-1H-indol-2- 217.5-218
493.3 yl)-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 522
6-(6-chloro-3-cyano-1-cyclopentyl-5-methyl-1H-indol-2- 186-187
511.0 yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 523
2-(6-chloro-3-cyano-1-cyclopentyl-5-methyl-1H-indol-2- 216.0-216.5
458- .2 yl)-N-(propan-2-yl)pyrimidine-5-sulfonamide 524
2-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2- 151-155 446.4
yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 525
6-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2- 181-185 435.3
yl]-N-[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 526
2-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N- 223-225 442.4
(propan-2-yl)pyrimidine-5-sulfonamide 527
2-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-(1,3- 250-253
478.2 difluoropropan-2-yl)pyrimidine-5-sulfonamide 528
2-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-[(1S)- 219-221
468.3- 1-cyclopropylethyl]pyrimidine-5-sulfonamide 529
2-[3-cyano-5-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N- 176-179 428.3
[(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide 530
2-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-[(1S)- 184-186
454.- 2 1-cyclopropylethyl]pyrimidine-5-sulfonamide 531
2-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]- 184-188
440.- 2 N-[(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide 535
6-[3-cyano-1-cyclopentyl-5-(difluoromethyl)-1H-indol-2- N/A 495.3
yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 536
2-[3-cyano-1-cyclopentyl-5-(difluoromethyl)-1H-indol-2- 176-177
496.3 yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 537
6-[3-cyano-1-cyclopentyl-5-(difluoromethyl)-1H-indol-2- 187-188
513.2 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 538
6-[3-cyano-1-cyclopentyl-5-(difluoromethyl)-1H-indol-2- 186-188
513.3 yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 544
2-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[(1S)- 178-181
440.3- 1-cyclopropylethyl]pyrimidine-5-sulfonamide 545
2-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[(1S)- 168-171
436.3- 1-cyclopropylethyl]pyrimidine-5-sulfonamide 546
2-[3-cyano-5-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N- 172-176 456.3
[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 547
2-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-[(2S)- 214-218
482.- 2 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 548
2-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H-indol-2-yl]- 175-180
468.- 3 N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-
sulfonamide 550 6-(3-cyano-1-cyclobutyl-5-methoxy-1H-indol-2-yl)-N-
149-150 461.2 (1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 551
2-(3-cyano-1-cyclobutyl-5-methoxy-1H-indol-2-yl)-N- 217-219 462.3
(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 560
6-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-[(2S)- 175-180
491.2- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 561
2-[3-cyano-1-(cyclopropylmethyl)-5-methyl-1H-indol-2- 174-178 436.3
yl]-N-[(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide 562
2-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N- 168-171 450.3
[(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide 563
2-[3-cyano-5-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N- 171-174 424.2
[(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide 564
6-[3-cyano-5-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N- 170-173 423.2
[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 565
2-[3-cyano-5-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N- 175-177 398.4
(propan-2-yl)pyrimidine-5-sulfonamide 566
2-[3-cyano-5-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N- 195-198 452.4
[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 567
2-[3-cyano-5-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N- 160-163 434.3
(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 569
2-(3-cyano-1-cyclobutyl-5-methoxy-1H-indol-2-yl)-N- 203-205 480.3
[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 570
2-(3-cyano-1-cyclobutyl-5-methoxy-1H-indol-2-yl)-N- 182-183 452.3
[(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide 571
6-(3-cyano-1-cyclopentyl-5-methoxy-1H-indol-2-yl)-N- 167-169 475.5
(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 572
2-(3-cyano-1-cyclopentyl-5-methoxy-1H-indol-2-yl)-N- 200-202 476.2
(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 590
6-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-1H-indol-2- 146-155
485.- 1 yl]-N-[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 591
2-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-1H-indol-2- N/A 496.1
yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 592
2-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-1H-indol-2- 168-175
486.- 1 yl]-N-[(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide 593
6-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol- 178-184
509.1- 2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 594
6-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol- N/A 499.1
2-yl]-N-[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 595
6-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol- 181-189
527.1- 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 596
6-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol- 194-199
541.1- 2-yl]-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-
sulfonamide 597
2-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol- 181-189
500.2- 2-yl]-N-[(1S)-1-cyclopropylethyl]pyrimidine-5- sulfonamide
598 2-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol-
204-218 474.1- 2-yl]-N-(propan-2-yl)pyrimidine-5-sulfonamide 599
2-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol- 174-210
510.1- 2-yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5- sulfonamide
600 2-[3-cyano-1-cyclopentyl-6-(2,2-difluoroethyl)-1H-indol-
240-246 528.1-
2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5- sulfonamide
603 2-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N- 217-222
428.3 (propan-2-yl)pyrimidine-5-sulfonamide 604
6-[3-cyano-5-fluoro-1-(propan-2-yl)-1H-indol-2-yl]-N- 138-143 427.3
[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 605
2-(3-cyano-1-cyclohexyl-6-methyl-1H-indol-2-yl)-N-[(2S)- 257-260
492.3- 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide 606
6-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-[(1S)- 169-174
463.2- 1-cyclopropylethyl]pyridine-3-sulfonamide 607
6-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N- 176-181 491.3
(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3- sulfonamide 616
6-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)- N/A 495.2
1H-indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3- sulfonamide
617 6-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)- N/A
485.2 1H-indol-2-yl]-N-[(1S)-1-cyclopropylethyl]pyridine-3-
sulfonamide 618
6-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)- N/A 513.1
1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 619
2-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)- 144-150
486.2 1H-indol-2-yl]-N-[(1S)-1-cyclopropylethyl]pyrimidine-5-
sulfonamide 620
2-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)- 152-161
485.1 1H-indol-2-yl]-N-(propan-2-yl)pyrimidine-5-sulfonamide 621
2-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)- 180-188
496.2 1H-indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5-
sulfonamide 622
2-[3-cyano-1-(cyclopropylmethyl)-6-(2,2-difluoroethyl)- 195-205
514.2 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyrimidine-5-sulfonamide 696
6-[3-cyano-1-cyclobutyl-5-(2,2-difluoroethyl)-1H-indol-2- N/A 471.2
yl]-N-(1-methylcyclopropyl)pyridine-3-sulfonamide 702
6-[3-cyano-1-cyclobutyl-5-(2,2-difluoroethyl)-1H-indol-2- 143-147
513.- 3 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide
Example 2
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-(1,3-difluoro-
propan-2-yl)pyridine-3-sulfonamide (Cpd 31)
##STR00211##
Step A: A solution of 6-methoxy-1H-indole (100.0 g, 679.0 mmol) in
DMF (560 mL) was cooled to -78.degree. C. and treated with
chlorosulfonyl isocyanate (71 mL, 815 mmol). After the addition the
reaction mixture was stirred for 1 hour. The dark solution was
poured into ice water (2 L) and the light brown solid was collected
by filtration, washed with additional water and dried to afford
6-methoxy-1H-indole-3-carbonitrile as a light brown solid (104.8 g,
90%).
##STR00212##
Step B: To 6-methoxy-1H-indole-3-carbonitrile (98.2 g, 0.57 mol)
was added cesium carbonate (430 g, 1.32 mol), DMF (165 mL) and
cyclobutylbromide (96%, 67.5 mL, 0.69 mol). The mixture was heated
to 90.degree. C. and stirred overnight. The mixture was cooled to
37.degree. C. and poured into ice water (500 mL), washing in with
water. After stirring for 1 hour the precipitate was collected on a
filter and dried under a stream of nitrogen to give
1-cyclobutyl-6-methoxy-1H-indole-3-carbonitrile as a tan solid
(124.1 g, 96%).
##STR00213##
Step C: 1-cyclobutyl-6-methoxy-1H-indole-3-carbonitrile (100 g, 442
mmol) was dissolved in CH.sub.2Cl.sub.2 (700 mL) and cooled to
-20.degree. C. Boron tribromide (300 g, 1.2 mol) was added dropwise
over 2.5 hours to the cooled solution. The reaction was poured into
ice water (2 L), neutralized to pH 7 with 5 N aq. sodium hydroxide
and stirred overnight at room temperature. The remaining organic
solvent was evaporated and the resulting suspension was filtered.
The solid was washed with water (2.times.200 mL), 1/1 hexane/ethyl
ether (2.times.125 mL) and dried in a stream of nitrogen to give
1-cyclobutyl-6-hydroxy-1H-indole-3-carbonitrile as a beige powder
(90.0 g, 96%).
##STR00214##
Step D: 1-cyclobutyl-6-hydroxy-1H-indole-3-carbonitrile (31.7 g,
149.5 mmol) was dissolved in 160 mL of isopropanol at 75.degree. C.
and CClF.sub.2H (gas) was bubbled into the reaction mixture via a
needle. To this mixture was added 20% aq. NaOH (40 mL) via an
addition funnel. Three additional portions of 20% aq. NaOH (40 mL)
were added every 30 minute. After 2 hours of total reaction time
the mixture was cooled to room temperature and the organic layer
was separated and concentrated. The aqueous layer was extracted
into ethyl acetate and the combined organic phases were washed with
brine and then dried over MgSO.sub.4, filtered and concentrated.
The residue was dissolved in 4/1 hexane/CH.sub.2Cl.sub.2 (800 mL)
and stirred with basic alumina (80 g, pH 9.5), and then filtered
and concentrated to yield a first crude fraction (28 g). The
alumina was washed with CH.sub.2Cl.sub.2 to provide a second crude
fraction (8.7 g) which was purified in the same manner to provide a
third crude fraction (4.0 g). The combined crude fractions were
again purified in the same manner to yield
1-cyclobutyl-6-(difluoromethoxy)-1H-indole-3-carbonitrile as a
white solid (28.3 g, 72%). .sup.1H NMR (CDCl.sub.3, 500 MHz):
.delta. 7.76 (1H, s), 7.72 (1H, d, J=8.5 Hz), 7.18 (1H, d, J=2 Hz),
7.12 (1H, dd, J=8.5 Hz, 2.0 Hz), 6.55 (1H, t, J=75 Hz), 4.82 (1H,
p, J=8 Hz), 2.66 (2H, m), 2.47 (2H, m), 2.01 (2H, m).
##STR00215##
Step E: Into a solution of
1-cyclobutyl-6-(difluoromethoxy)-1H-indole-3-carbonitrile (1.5 g,
5.7 mmol) and triisopropyl borate (2.4 mL, 10.3 mmol) in THF (25
mL) at -78.degree. C. was added LDA (1.5 M in cyclohexane, 5.0 mL,
7.5 mmol). The mixture was stirred at -78.degree. C. for 30 min and
then quenched with ice water (60 mL) and stirred for 15 min without
cooling. The mixture was extracted with ethyl acetate 1:1 in hexane
(20 mL). The aqueous layer was acidified with 2 N aq. HCl to pH 5
and extracted with CH.sub.2Cl.sub.2 (60 mL). The organic layer was
dried over Na.sub.2SO.sub.4 and concentrated to give
3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-ylboronic acid
as a solid (1.8 g, 60% pure by LCMS) that was used in the next step
without further purification.
##STR00216##
Step F: A mixture of
3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-ylboronic acid
(0.68 g, 1.33 mmol),
6-chloro-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide (0.25 g,
0.93 mmol), tri-tert-butylphosphonium tetrafluoroborate (22 mg,
0.076 mmol) and Pd.sub.2(dba).sub.3 (34 mg, 0.037 mmol) and
potassium fluoride (0.17 g, 2.93 mmol) in THF (8.0 mL) was stirred
at 35.degree. C. overnight. The solvent was then evaporated and the
residue was purified by flash chromatography with 0-10% ethyl
acetate in CH.sub.2Cl.sub.2 to provide the title Compound 31 as a
solid (210 mg, 46%). Melting point: 159-161; MS m/z 497.0
M+H.sup.+; .sup.1H NMR (500 MHz, CDCl.sub.3): .delta. 9.25 (1H, dd,
J=2.2 Hz, J=0.6 Hz), 8.37 (1H, dd, J=8.2 Hz, J=2.3 Hz), 8.03 (1H,
dd, J=8.3 Hz, J=0.8 Hz), 7.80 (1H, d, J=8.7 Hz), 7.50 (1H, d, J=1.9
Hz), 7.18 (1H, dd, J=8.6 Hz, J=1.9 Hz), 6.60 (1H, t, J=3.7 Hz),
5.37-5.33 (1H, m), 5.20 (1H, d, J=9.2 Hz), 4.64-4.46 (4H, m),
3.96-3.90 (1H, m), 2.62-2.55 (2H, m), 2.46-2.40 (2H, m), 1.95-1.88
(2H, m).
Additional compounds representative of the present invention may be
prepared according to the procedure of Example 2 by substituting
the appropriate starting materials, reagents and reaction
conditions and include compounds selected from (wherein MS
represents mass spec as MH.sup.+, unless otherwise indicated, m.p.
represents melting point in .degree. C., and N/A indicates that the
data was not obtained):
TABLE-US-00006 Cpd Name m.p. MS 1
6-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H- 157-159 449.1
indol-2-yl]-N-(propan-2-yl)pyridine-3-sulfonamide 2
6-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H- 130-132 461.4
indol-2-yl]-N-cyclobutylpyridine-3-sulfonamide 3
6-[3-cyano-6-(difluoromethoxy)-1-propyl-1H-indol-2-yl]- 166-170
449.3 N-(propan-2-yl)pyridine-3-sulfonamide 4
5-[3-cyano-1-cyclobutyl-6-(cyclobutyloxy)-1H-indol-2-yl]- 178-180
465.3 N-(propan-2-yl)pyridine-2-sulfonamide 10
6-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2- 191-193
479.1 yl]-N-(propan-2-yl)pyridine-3-sulfonamide 11
6-[3-cyano-1-(cyclopropylmethyl)-6-(trifluoromethoxy)- 203-205
479.3 1H-indol-2-yl]-N-(propan-2-yl)pyridine-3-sulfonamide 12
6-[3-cyano-1-(propan-2-yl)-6-(trifluoromethoxy)-1H- 160-162 467.3
indol-2-yl]-N-(propan-2-yl)pyridine-3-sulfonamide 13
6-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)- 154-156 461.3
1H-indol-2-yl]-N-(propan-2-yl)pyridine-3-sulfonamide 16
6-[3-cyano-1-cyclobutyl-6-(propan-2-ylsulfanyl)-1H- 129-131 469.2
indol-2-yl]-N-(propan-2-yl)pyridine-3-sulfonamide 17
6-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol- N/A 493.1
2-yl]-N-(propan-2-yl)pyridine-3-sulfonamide 18
N-tert-butyl-6-[3-cyano-1-cyclopentyl-6- 182-184 507.1
(trifluoromethoxy)-1H-indol-2-yl]pyridine-3-sulfonamide 19
6-[3-cyano-1-cyclobutyl-5-(difluoromethoxy)-1H-indol-2- 148-153
461.3 yl]-N-(propan-2-yl)pyridine-3-sulfonamide 20
N-tert-butyl-6-[3-cyano-1-cyclobutyl-5- 167-170 475.3
(difluoromethoxy)-1H-indol-2-yl]pyridine-3-sulfonamide 21
6-[3-cyano-1-cyclopentyl-5-(difluoromethoxy)-1H-indol- 177-179
475.2 2-yl]-N-(propan-2-yl)pyridine-3-sulfonamide 22
1-cyclobutyl-2-[5-(piperidin-1-ylsulfonyl)pyridin-2-yl]-6- 169-171
495.- 2 (propan-2-ylsulfanyl)-1H-indole-3-carbonitrile 23
6-[3-cyano-1-cyclobutyl-5-(trifluoromethoxy)-1H-indol-2- 174-176
479.3 yl]-N-(propan-2-yl)pyridine-3-sulfonamide 24
6-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2- 158-160
515.2 yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 25
6-[3-cyano-1-cyclobutyl-5-(trifluoromethoxy)-1H-indol-2- 179-182
515.3 yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 26
5-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2- N/A 479.2
yl]-N-(propan-2-yl)pyridine-2-sulfonamide 32
6-[3-cyano-1-cyclobutyl-5-(difluoromethoxy)-1H-indol-2- 166-172
497.1 yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 33
6-[3-cyano-1-cyclopentyl-5-(difluoromethoxy)-1H-indol- 172-175
511.1 2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 34
6-[3-cyano-1-cyclopentyl-5-(trifluoromethoxy)-1H-indol- 159-160
529.3 2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 36
6-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H- 142-145 485.1
indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3- sulfonamide 39
5-[3-cyano-1-cyclopropyl-6-(difluoromethoxy)-1H-indol- 209-210
447.7 2-yl]-N-(propan-2-yl)pyridine-2-sulfonamide 40
5-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)- 186-188 461.2
1H-indol-2-yl]-N-(propan-2-yl)pyridine-2-sulfonamide 41
6-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)- 150-151 497.2
1H-indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3- sulfonamide
42 6-[3-cyano-1-cyclopropyl-6-(difluoromethoxy)-1H-indol- 219-220
483.0 2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 43
6-[3-cyano-1-cyclobutyl-6-(propan-2-yl)-1H-indol-2-yl]- 135-140
473.3 N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 44
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N- 144-145 457.2
(M - H) (1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 45
6-[3-cyano-6-(difluoromethoxy)-1-propyl-1H-indol-2-yl]- 156-158
485.2 N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 48
6-(3-cyano-1-cyclobutyl-6-ethyl-1H-indol-2-yl)-N-(1,3- 201-202
459.0 difluoropropan-2-yl)pyridine-3-sulfonamide 49
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol- 177-178
511.3 2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 51
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2- 158-159
461.1 yl]-N-(propan-2-yl)pyridine-3-sulfonamide 52
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol- 157-158
475.2 2-yl]-N-(propan-2-yl)pyridine-3-sulfonamide 53
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol- 189-195
529.1 2-yl]-N-(1,1,1-trifluoropropan-2-yl)pyridine-3- sulfonamide
54 6-{3-cyano-6-methyl-1-[(3R)-tetrahydrofuran-3-yl]-1H- 152-153
461.2 indol-2-yl}-N-(1,3-difluoropropan-2-yl)pyridine-3-
sulfonamide 55
6-{3-cyano-6-methyl-1-[(3R)-tetrahydrofuran-3-yl]-1H- 164-167 425.2
indol-2-yl}-N-(propan-2-yl)pyridine-3-sulfonamide 59
6-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethoxy)-1H-indol- 171-173
475.1 2-yl]-N-(propan-2-yl)pyridine-3-sulfonamide 67
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol- 224-229
507.4 2-yl]-N-(1-fluoro-2-methylpropan-2-yl)pyridine-3- sulfonamide
68 6-[3-cyano-1-(cyclopropylmethyl)-6-(trifluoromethoxy)- 132-133
515.0 1H-indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-
sulfonamide 69 6-[3-cyano-1-(propan-2-yl)-6-(trifluoromethoxy)-1H-
116-117 503.3 indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-
sulfonamide 70
6-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol- 141-143
529.3 2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 74
2-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N- 213-214 424.4
(propan-2-yl)pyrimidine-5-sulfonamide 75
6-[3-cyano-6-ethyl-1-(propan-2-yl)-1H-indol-2-yl]-N- 185-186 411.0
(propan-2-yl)pyridine-3-sulfonamide 77
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2- 171-178
493.4 yl]-N-(1-fluoro-2-methylpropan-2-yl)pyridine-3- sulfonamide
78 6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2- 159-165
515.0 yl]-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide 80
6-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N- 188-195 433.0
(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 81
6-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2- 175-182 445.0
yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 82
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(1,3- N/A 445.0
difluoropropan-2-yl)pyridine-3-sulfonamide 93
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2- 182-187
527.0 yl]-N-[1-(trifluoromethyl)cyclopropyl]pyridine-3- sulfonamide
94 6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol- 186-193
541.0 2-yl]-N-[1-(trifluoromethyl)cyclopropyl]pyridine-3-
sulfonamide 98 2-(3-cyano-1-cyclohexyl-6-methyl-1H-indol-2-yl)-N-
196-201 438.0 (propan-2-yl)pyrimidine-5-sulfonamide 99
6-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2- 187-190
489.0 yl]-N-(propan-2-yl)pyridine-3-sulfonamide 100
6-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2- 175-178
525.0 yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 103
6-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethenyl)-1H-indol- N/A 492.9
2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 105
6-[3-cyano-1-cyclohexyl-6-(trifluoromethoxy)-1H-indol-2- 146-148
542.8- yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 106
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2- 162-168
541.0 yl]-N-[1-(trifluoromethyl)cyclobutyl]pyridine-3- sulfonamide
116 2-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2-
200-203 480.7- yl]-N-(propan-2-yl)pyrimidine-5-sulfonamide 117
2-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol- 216-218
494.0 2-yl]-N-(propan-2-yl)pyrimidine-5-sulfonamide 121
2-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N- 134-138 410.2
(propan-2-yl)pyrimidine-5-sulfonamide 122
2-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-(1,3- 140-145
446.0 difluoropropan-2-yl)pyrimidine-5-sulfonamide 127
2-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2- 192-194
462.0 yl]-N-(propan-2-yl)pyrimidine-5-sulfonamide 128
2-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2- 227-229
515.9 yl]-N-(1,1,1-trifluoropropan-2-yl)pyrimidine-5- sulfonamide
129 2-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2- 205-207
497.9 yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 132
2-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(1,3- 236-238
446.0 difluoropropan-2-yl)pyrimidine-5-sulfonamide 133
2-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2- 261-262 446.0
yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 134
2-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N- 213-215 433.9
(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 135
2-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N- 229-231 460.0
(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 136
2-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)- 207-209 497.9
1H-indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5- sulfonamide
137 2-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H- 219-221
485.9 indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5-
sulfonamide 158 6-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-
168-173 459.2 (1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 159
2-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N- 193-198 424.2
(propan-2-yl)pyrimidine-5-sulfonamide 160
2-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N- 202-207 460.0
(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 161
6-[3-cyano-1-cyclobutyl-6-(methylsulfanyl)-1H-indol-2- 182-186
488.9 yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 162
2-[3-cyano-1-cyclobutyl-6-(methylsulfanyl)-1H-indol-2- 199-201
478.1 yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 167
2-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N- 205-206 398.1
(propan-2-yl)pyrimidine-5-sulfonamide 168
2-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2- 245-247 410.1
yl]-N-(propan-2-yl)pyrimidine-5-sulfonamide 169
2-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N- 217-219 410.0
(propan-2-yl)pyrimidine-5-sulfonamide 170
2-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)- 182-184 462.0
1H-indol-2-yl]-N-(propan-2-yl)pyrimidine-5-sulfonamide 171
2-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H- 193-196 450.1
indol-2-yl]-N-(propan-2-yl)pyrimidine-5-sulfonamide 172
2-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N- 200-202 426.0
(propan-2-yl)pyrimidine-5-sulfonamide 177
2-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2- 202-204
515.9- yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 178
2-[3-cyano-1-cyclopentyl-6-(trifluoromethoxy)-1H-indol- 181-187
529.9 2-yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5- sulfonamide
179 2-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2- 174-176
526.0 yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 185
2-[3-cyano-1-cyclobutyl-6-(propan-2-yl)-1H-indol-2-yl]- 220-222
438.2 N-(propan-2-yl)pyrimidine-5-sulfonamide 186
2-[3-cyano-1-cyclobutyl-6-(propan-2-yl)-1H-indol-2-yl]- 214-222
474.2 N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 190
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[1- 199-210
489.1 (trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide 198
2-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-(1,3- 211-215
474.1 difluoropropan-2-yl)pyrimidine-5-sulfonamide 199
6-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N-(1,3- 210-215
473.5 difluoropropan-2-yl)pyridine-3-sulfonamide 200
2-(3-cyano-1-cyclohexyl-5-methyl-1H-indol-2-yl)-N- 183-188 438.1
(propan-2-yl)pyrimidine-5-sulfonamide 229
6-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N- 174-177 461.2
(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 230
2-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N- 217-219 462.1
(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 231
2-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N- 232-234 476.1
(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 232
2-[3-cyano-6-(difluoromethoxy)-1-propyl-1H-indol-2-yl]- 177-179
486.0 N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 233
2-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol- 199-201
512.0 2-yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5- sulfonamide
239 6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2- 132-135
493.1 yl]-N-(1,3-dihydroxypropan-2-yl)pyridine-3-sulfonamide 241
2-(3-cyano-1-cyclohexyl-6-methyl-1H-indol-2-yl)-N-(1,3- 225-230
474.0 difluoropropan-2-yl)pyrimidine-5-sulfonamide 242
2-[3-cyano-5-(difluoromethoxy)-1-ethyl-1H-indol-2-yl]-N- 180-185
436.2- (propan-2-yl)pyrimidine-5-sulfonamide 245
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-(3,3- 165-166
457.1 difluorocyclobutyl)pyridine-3-sulfonamide 246
6-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N- N/A 487.0
(3,3-difluorocyclobutyl)pyridine-3-sulfonamide 253
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-[1- 214-218
503.1 (trifluoromethyl)cyclobutyl]pyridine-3-sulfonamide 255
6-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2- 191-195 475.0
yl]-N-[1-(trifluoromethyl)cyclopropyl]pyridine-3- sulfonamide 256
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[1- 189-194 475.1
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide 258
6-(3-cyano-1-cyclobutyl-5-ethyl-1H-indol-2-yl)-N-(1,3- 163-164
459.2 difluoropropan-2-yl)pyridine-3-sulfonamide 267
6-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-1H-indol-2- 166-168
495.- 0 yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 268
N-{5-[3-cyano-1-cyclobutyl-6-(pyrimidin-2-yloxy)-1H- 275-277 503.3
indol-2-yl]pyridin-2-yl}-2-methylpropane-2-sulfonamide 269
N-{5-[3-cyano-1-(cyclopropylmethyl)-6- 214-215 475.3
(difluoromethoxy)-1H-indol-2-yl]pyridin-2-yl}-2-
methylpropane-2-sulfonamide 270
N-{6-[3-cyano-1-(cyclopropylmethyl)-6- 156-158 459.3
(difluoromethoxy)-1H-indol-2-yl]pyridin-3-
yl}cyclopropanesulfonamide 271
N-{6-[3-cyano-1-cyclobutyl-6-(pyrimidin-2-yloxy)-1H- 206-208 489.2
indol-2-yl]pyridin-3-yl}propane-1-sulfonamide 272
N-(6-{3-cyano-6-[(3-cyanopyridin-2-yl)oxy]-1-cyclobutyl- 199-201
513.3-
1H-indol-2-yl}pyridin-3-yl)propane-1-sulfonamide 273
N-(6-{3-cyano-6-[(3-cyanopyrazin-2-yl)oxy]-1-cyclobutyl- 252-254
514.2- 1H-indol-2-yl}pyridin-3-yl)propane-1-sulfonamide 274
N-{6-[3-cyano-1-cyclobutyl-6-(propan-2-yloxy)-1H-indol- 175-177
452.3 2-yl]pyridazin-3-yl}cyclopropanesulfonamide 275
N-{6-[3-cyano-1-cyclobutyl-6-(propan-2-yloxy)-1H-indol- 225-227
426.3 2-yl]pyridazin-3-yl}methanesulfonamide 276
N-{6-[3-cyano-1-cyclobutyl-6-(propan-2-yloxy)-1H-indol- 181-183
440.4 2-yl]pyridazin-3-yl}ethanesulfonamide 277
N-[6-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2- 212-214 412.3
yl)pyridazin-3-yl]ethanesulfonamide 278
N-[6-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2- 218-220 440.3
yl)pyridazin-3-yl]-2-methylpropane-2-sulfonamide 279
N-{6-[3-cyano-1-(cyclopropylmethyl)-6-(propan-2-yloxy)- 149-154
439.9 1H-indol-2-yl]pyridin-3-yl}ethanesulfonamide 280
N-{6-[3-cyano-1-(cyclopropylmethyl)-6-(propan-2-yloxy)- 150-155
451.1 1H-indol-2-yl]pyridin-3-yl}cyclopropanesulfonamide 281
N-{6-[3-cyano-1-(cyclopropylmethyl)-6-(propan-2-yloxy)- 168-172
453.5 1H-indol-2-yl]pyridin-3-yl}propane-2-sulfonamide 282
N-{6-[3-cyano-1-ethyl-6-(propan-2-yloxy)-1H-indol-2- 170-175 455.2
yl]pyridin-3-yl}-N-(propan-2-yl)ethanesulfonamide 283
N-{6-[3-cyano-1-(cyclopropylmethyl)-6-(2,2,2- 188-193 493.3
trifluoroethoxy)-1H-indol-2-yl]pyridin-3-yl}propane-2- sulfonamide
284 N-{6-[3-cyano-1-(cyclopropylmethyl)-6-(2,2,2- 190-195 479.3
trifluoroethoxy)-1H-indol-2-yl]pyridin-3- yl}ethanesulfonamide 285
N-{6-[3-cyano-1-ethyl-6-(propan-2-yloxy)-1H-indol-2- 180-185 425.3
yl]pyridin-3-yl}cyclopropanesulfonamide 286
N-{6-[3-cyano-1-ethyl-6-(propan-2-yloxy)-1H-indol-2- 180-185 427.2
yl]pyridin-3-yl}propane-2-sulfonamide 290
N-{5-[3-cyano-1-(cyclopropylmethyl)-6-(2,2,2- N/A 479.3
trifluoroethoxy)-1H-indol-2-yl]pyridin-2- yl}ethanesulfonamide 291
N-{5-[3-cyano-1-(cyclopropylmethyl)-6-(2,2,2- N/A 493.3
trifluoroethoxy)-1H-indol-2-yl]pyridin-2-yl}propane-2- sulfonamide
292 N-{5-[3-cyano-1-ethyl-6-(propan-2-yloxy)-1H-indol-2- 232-235
489.1 yl]pyridin-2-yl}-N-(2,2-
difluoroethyl)cyclopropanesulfonamide 293
N-{5-[3-cyano-1-ethyl-6-(propan-2-yloxy)-1H-indol-2- 212-214 469.3
yl]pyridin-2-yl}-N-(2- hydroxyethyl)cyclopropanesulfonamide 294
N-{5-[3-cyano-1-ethyl-6-(propan-2-yloxy)-1H-indol-2- 236-238 464.1
yl]pyridin-2-yl}-N- (cyanomethyl)cyclopropanesulfonamide 295
N-{5-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H- 239-240 475.3
indol-2-yl]pyridin-2-yl}-2-methylpropane-2-sulfonamide 296
N-[6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2- 241-245 421.2
yl)pyridin-3-yl]cyclopropanesulfonamide 297
N-[6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2- 200-205 407.1
yl)pyridin-3-yl]cyclopropanesulfonamide 299
N-{5-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H- 263-264 462.5
indol-2-yl]pyridin-2-yl}-2-methylpropane-2-sulfonamide 301
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2- 188-190
472.1 yl]-N-(1-cyanoethyl)pyridine-3-sulfonamide 304
6-[3-cyano-1-cyclohexyl-6-(trifluoromethoxy)-1H-indol-2- 181-183
561.0- yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 305
6-[3-cyano-1-cyclohexyl-6-(trifluoromethoxy)-1H-indol-2- 195-197
533.2- yl]-N-[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 323
2-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2- 221-223
516.2 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-
sulfonamide 326
2-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol- 231-232
530.2 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-
sulfonamide 341
6-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2- 149-151
543.0 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 359 6-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H-
163-166 503.1
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 398
2-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)- 211-212 516.2
1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyrimidine-5-sulfonamide 399
2-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H- 219-221 504.3
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-
5-sulfonamide 400
2-[3-cyano-6-(difluoromethoxy)-1-propyl-1H-indol-2-yl]- 207-208
504.2 N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5- sulfonamide
471 2-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2- 150-152
516.0 yl]-N-[(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide 472
2-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2- 187-189
544.0 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-
sulfonamide 473
2-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2- 176-179
490.0 yl]-N-(propan-2-yl)pyrimidine-5-sulfonamide 543
N-tert-butyl-6-[3-cyano-1-cyclobutyl-6- 178-180 475.3
(difluoromethoxy)-1H-indol-2-yl]pyridine-3-sulfonamide
Example 3
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(1,3-difluoropr-
opan-2-yl)pyridine-3-sulfonamide (Cpd 108)
##STR00217##
Step A: Into a solution of 4-fluoro-3-methylaniline (8.75 g, 70
mmol) in methanol (65 mL) and water (65 mL) was added sodium
bicarbonate (5.88 g, 70 mmol) followed by portionwise addition of
powdered I.sub.2 (17.78 g, 70 mmol). The mixture was stirred at
room temperature overnight then treated with water (300 mL). The
aqueous mixture was extracted with CH.sub.2Cl.sub.2 (3.times.200
mL). The organics were combined and washed with sat. aq. sodium
thiosulfate, water, and brine. The mixture was dried over
Na.sub.2SO.sub.4 and concentrated. The residue was purified by
flash chromatography with 30-100% CH.sub.2Cl.sub.2/hexane to give
4-fluoro-2-iodo-5-methylaniline (12.1 g, 69%), which contained
.about.10% of the undesired isomer
(4-fluoro-2-iodo-3-methylaniline).
##STR00218##
Step B: Into a mixture of 4-fluoro-2-iodo-5-methylaniline (12.0 g,
47.8 mmol, plus ca. 10% of the undesired isomer),
PdCl.sub.2(PPh.sub.3).sub.2 (1.68 g, 2.39 mmol) and copper(I)
iodide (0.455 g, 2.39 mmol) in triethylamine (125 mL) at 0.degree.
C. was added trimethylsilylacetylene (5.15 g, 52.6 mmol) dropwise.
The mixture was warmed to room temperature and stirred overnight.
The solvent was evaporated and the residue was dissolved in ethyl
ether and filtered. The filtrate was evaporated and purified via
flash chromatography with 5-35% ethyl acetate in hexane to give
4-fluoro-5-methyl-2-((trimethylsilyl)ethynyl)aniline (10.3 g, 97%),
which contained .about.10% of the undesired isomer
(4-fluoro-3-methyl-2-((trimethylsilyl)ethynyl)aniline).
##STR00219##
Step C: A mixture of
4-fluoro-5-methyl-2-((trimethylsilyl)ethynyl)aniline (plus ca. 10%
of the undesired isomer) (10.3 g, 46.6 mmol) and copper(I) iodide
(17.75 g, 93.2 mmol) in DMF (200 mL) was stirred at 100.degree. C.
for 4 hours. The mixture was then treated with ethyl ether (300 mL)
and filtered. The filtrate was washed with water (200 mL) and
extracted with ether. The organics were combined and washed with
water, brine, and dried over Na.sub.2SO.sub.4 and concentrated. The
residue was purified by flash chromatography with 5-35% ethyl
acetate in hexane to give 1.9 g
5-fluoro-6-methyl-2-(trimethylsilyl)-1H-indole containing
.about.10% of the undesired isomer,
5-fluoro-4-methyl-2-(trimethylsilyl)-1H-indole plus desilylated
product, 5-fluoro-6-methyl-1H-indole (2.8 g) with .about.10% of the
undesired isomer, 5-fluoro-4-methyl-1H-indole. Silylated material,
5-fluoro-6-methyl-2-(trimethylsilyl)-1H-indole containing
.about.10% of the undesired isomer, was re-dissolved in methanol
(20 mL) and stirred with potassium carbonate overnight, filtered
and concentrated. All desilylated material was combined (3.7 g) and
recrystallized from CH.sub.2Cl.sub.2 and hexane to provide
5-fluoro-6-methyl-1H-indole (1.9 g).
##STR00220##
Step D: Into a solution of 5-fluoro-6-methyl-1H-indole (1.9 g, 12.8
mmol) in DMF (13 mL) at -78.degree. C. was added chlorosulfonyl
isocyanate (1.33 mL, 15.3 mmol). After addition the cooling bath
was removed and the mixture was allowed to warm to room
temperature. The mixture was then poured into ice water, filtered
and washed with water and brine. The cake was then dissolved in
acetonitrile and concentrated to give
5-fluoro-6-methyl-1H-indole-3-carbonitrile (2.2 g, 100%).
##STR00221##
Step E: A mixture of 5-fluoro-6-methyl-1H-indole-3-carbonitrile
(1.0 g, 5.8 mmol), cyclobutylbromide (0.81 mL, 8.6 mmol) and cesium
carbonate (3.9 g, 12.1 mmol) in DMF (10 mL) was stirred at
90.degree. C. overnight. The mixture was then poured into ice water
and extracted with ethyl acetate. The organics were combined and
washed with water, brine and dried over Na.sub.2SO.sub.4 and
evaporated. The residue was purified by flash chromatography with
5-35% ethyl acetate in hexane to give
1-cyclobutyl-5-fluoro-6-methyl-1H-indole-3-carbonitrile (1.2 g,
92%). .sup.1H NMR (500 MHz, CDCl.sub.3): 7.68 (1H, s), 7.35 (1H, d,
J=9.6 Hz), 7.17 (1H, d, J=6.1 Hz), 4.83-4.79 (1H, m), 2.68-2.60
(2H, m), 2.48-2.37 (5H, m), 2.05-1.96 (2H, m).
##STR00222##
Step F: Into a solution of
1-cyclobutyl-5-fluoro-6-methyl-1H-indole-3-carbonitrile (1.2 g, 5.3
mmol) and triisopropyl borate (2.18 mL, 9.47 mmol) in THF (20 mL)
at -78.degree. C. was added LDA (1.5 M in cyclohexane, 4.6 mL, 6.84
mmol). The mixture was stirred at -78.degree. C. for 30 min and
quenched with ice water (60 mL) and stirred for 15 min without
cooling. The mixture was extracted with ethyl acetate 1:1 in hexane
(20 mL). The aqueous layer was acidified with 2 N aq. HCl to pH 5
and then extracted with CH.sub.2Cl.sub.2 (60 mL). The organic layer
was dried over Na.sub.2SO.sub.4 and concentrated to give
3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-ylboronic acid as
a solid (1.44 g, 98% pure by LCMS) that was used in the next step
without further purification.
##STR00223##
Step G: A mixture of
3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-ylboronic acid
(0.45 g, 1.5 mmol),
6-chloro-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide (0.27 g,
1.0 mmol), tri-tert-butylphosphonium tetrafluoroborate (29 mg, 0.1
mmol) and Pd.sub.2(dba).sub.3 (46 mg, 0.05 mmol) and potassium
fluoride (0.23 g, 4.0 mmol) in THF (5.0 mL) was stirred at
40.degree. C. overnight. The solvent was then evaporated and the
residue was purified by flash chromatography with 0-10% ethyl
acetate in CH.sub.2Cl.sub.2 to provide the title Compound 108 (220
mg, 48%). Melting point: 186-188; MS m/z 463.0 M+H.sup.+; .sup.1H
NMR (500 MHz, CDCl.sub.3): .delta. 9.24 (1H, d, J=1.7 Hz), 8.35
(1H, dd, J=8.3 Hz, J=2.3 Hz), 8.02 (1H, d, J=8.2 Hz), 7.51 (1H, d,
J=6.0 Hz), 7.42 (1H, dd, J=9.2 Hz), 5.35-5.20 (1H, m), 5.19 (1H, d,
J=9.0 Hz), 4.63-4.45 (4H, m), 3.94-3.90 (1H, m), 2.65-2.59 (2H, m),
2.59 (3H, s), 2.48-2.40 (2H, m), 1.95-1.87 (2H, m).
Additional compounds representative of the present invention may be
prepared according to the procedure of Example 3 by substituting
the appropriate starting materials, reagents and reaction
conditions and include compounds selected from (wherein MS
represents mass spec as MH.sup.+, unless otherwise indicated, and
m.p. represents melting point in .degree. C.):
TABLE-US-00007 Cpd Name m.p. MS 50
6-(6-chloro-3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)- 211-213
482.8- N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 101
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methoxy-1H-indol-2- 234-237
443.0 yl)-N-(propan-2-yl)pyridine-3-sulfonamide 102
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methoxy-1H-indol-2- 217-219
478.9 yl)-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 107
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-5-fluoro-1H-indol- 182-186
488.9- 2-yl)-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 110
6-[6-chloro-3-cyano-1-(cyclopropylmethyl)-5-fluoro-1H- 202-204
483.0 indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-
sulfonamide 145
2-(3-cyano-1-cyclobutyl-6-cyclopropyl-5-fluoro-1H-indol- 237-238
477.0- 2-yl)-N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide
146 2-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-
243-249 464.- 1 N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide
149 2-(6-chloro-3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-
>245 483.- 9 N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide
decomp. 150 2-(3-cyano-1-cyclobutyl-5-fluoro-6-methoxy-1H-indol-2-
245-247 480.0
yl)-N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 225
6-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-6-methoxy-1H- 196-199
479.0 indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-
sulfonamide
Example 4
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-yl]-N-[(2S)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide (Cpd 300)
##STR00224##
Step A: 2-chloropyridine-5-sulfonyl chloride (12 g, 56.6 mmol) was
added to a solution of (S)-1,1,1-trifluoropropan-2-amine
hydrochloride (7.8 g, 51.2 mmol) in pyridine (15 mL) at 0.degree.
C. The mixture was stirred at room temperature for 10 minutes and
diluted with ethyl acetate (200 ml) and washed with 3 N aq. HCl
(2.times.100 mL). The organic layer was dried over
Na.sub.2SO.sub.4, filtered, and concentrated. The solid was
triturated with hexane (2.times.40 mL) and filtered to provide
(S)-6-chloro-pyridine-3-sulfonic acid
(2,2,2-trifluoro-1-methyl-ethyl)-amide as an off-white solid (11.84
g, 75%). .sup.1H NMR (500 MHz, CDCl.sub.3): .delta.0.81 (1H, d,
J=2.4 Hz), 8.18 (1H, dd, J=2.5 Hz, 2.6 Hz), 7.51 (1H, d, J=8.8 Hz),
4.92 (1H, br s), 4.08 (1H, m), 1.45 (3H, d, J=7.0 Hz).
##STR00225##
Step B: To 1-cyclobutyl-6-difluoromethoxy-1H-indole-3-carbonitrile
(830 mg, 3.17 mmol) in THF (10 mL) was added tributyltin iodide
(1.13 mL, 4.04 mmol) and the solution cooled to -78.degree. C. A
solution of LDA (1.5M in cyclohexane, 3.4 mL, 5.1 mmol) was added
dropwise. After complete addition the bath was removed and the
mixture stirred at room temperature for 1 hour. THF was then
removed under vacuum and the residue filtered through silica gel
using CH.sub.2Cl.sub.2 as an eluant and the mixture concentrated.
The residue was purified by flash chromatography using 30-50%
CH.sub.2Cl.sub.2/hexanes to provide
1-cyclobutyl-6-difluoromethoxy-2-tributylstannanyl-1H-indole-3-carbonitri-
le as a clear, colorless oil (1.23 g, 70%).
##STR00226##
Step C:
1-cyclobutyl-6-difluoromethoxy-2-tributylstannanyl-1H-indole-3-ca-
rbonitrile (650 mg, 1.17 mmol) was combined with
(S)-6-chloro-pyridine-3-sulfonic acid
(2,2,2-trifluoro-1-methyl-ethyl)-amide (338 mg, 1.17 mmol, >98%
ee), cuprous iodide (68 mg, 0.36 mmol), and
tetrakis(triphenylphosphine)palladium (105 mg, 0.091 mmol) under
nitrogen. Dioxane (2.6 mL) was added and the mixture stirred at
100.degree. C. for 1 hour. The mixture was diluted in ethyl acetate
(50 mL) and filtered. The filtrate was concentrated under vacuum
and purified by two successive silica gel chromatographic
separations (5% ethyl acetate in CH.sub.2Cl.sub.2; then 20% ethyl
acetate in hexanes). Triturating with 1/1 hexanes/ethyl ether
yielded the title Compound 300 as a white solid (260 mg, 43%).
Melting point: 159-162; MS m/z 515.4 M+H.sup.+; .sup.1H NMR
(CDCl.sub.3, 500 MHz): .delta. 9.23 (1H, d, J=2 Hz), 8.34 (1H, dd,
J=8.0 Hz, 2.5 Hz), 8.03 (1H, d, J=8.0 Hz), 7.80 (1H, d, J=8.5 Hz),
7.49 (1H, d, J=1.5 Hz), 7.17 (1H, dd, J=8.5 Hz, 2 Hz), 6.59 (1H, t,
J=75 Hz), 5.35 (1H, p, J=8.5 Hz), 4.98 (1H, br s), 4.17
Additional compounds representative of the present invention may be
prepared according to the procedure of Example 4 by substituting
the appropriate starting materials, reagents and reaction
conditions and include compounds selected from (wherein MS
represents mass spec as MH.sup.+, unless otherwise indicated, m.p.
represents melting point in .degree. C., and N/A indicates that the
data was not obtained):
TABLE-US-00008 Cpd Name m.p. MS 118
6-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N- N/A 469.5
[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 119
6-(5-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(1S)- 154-155
455.0- 1-cyclopropylethyl]pyridine-3-sulfonamide 130
2-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2- 172-174
488.0 yl]-N-[(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide 131
2-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N- 165-167
462.0 [(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide 142
6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[(1S)- 128-130
439.0- 1-cyclopropylethyl]pyridine-3-sulfonamide 143
6-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N- 159-160 453.0
[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 144
6-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-[(1S)- 136-138
439.0- 1-cyclopropylethyl]pyridine-3-sulfonamide 151
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2- 163-168
487.1 yl]-N-[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 152
6-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2- N/A 505.0
yl]-N-[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 154
6-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(1S)- N/A 454.9
1-cyclopropylethyl]pyridine-3-sulfonamide 155
6-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N- N/A 469.0
[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 174
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol- 176-182
501.3 2-yl]-N-[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 180
2-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N- 211-212
490.1 [(2R)-1,1,1-trifluoropropan-2-yl]pyrimidine-5- sulfonamide
181 2-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(2R)-
143-145 464.0- 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide
182 2-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N- 116-118
478.0 [(2R)-1,1,1-trifluoropropan-2-yl]pyrimidine-5- sulfonamide
183 2-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N- 147-149
480.0 [(2R)-1,1,1-trifluoropropan-2-yl]pyrimidine-5- sulfonamide
184 2-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2- 112-114
516.1 yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-
sulfonamide 191
6-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2- 171-177
533.1- yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 192
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(2R)- 204-208
463.0- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 194
6-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H- 166-168 503.0
indol-2-yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 195
6-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-1H-indol-2- 170-172
543.0 yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 196
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2- 159-164
515.0 yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 197
6-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2- 165-169 463.0
yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide 201
6-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[(1S)- 173-178
435.1- 1-cyclopropylethyl]pyridine-3-sulfonamide 202
2-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(1S)- 129-131
136.1- 1-cyclopropylethyl]pyrimidine-5-sulfonamide 203
2-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2- 205-207 436.0
yl]-N-[(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide 204
2-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N- 180-182 450.1
[(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide 205
2-(3-cyano-1-cyclobutyl-6-methoxy-1H-indol-2-yl)-N- 204-206 452.0
[(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide 206
2-(3-cyano-1-cyclopentyl-6-methoxy-1H-indol-2-yl)-N- 192-194 466.0
[(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide 207
2-[3-cyano-6-(difluoromethoxy)-1-(propan-2-yl)-1H- 169-170 476.0
indol-2-yl]-N-[(1S)-1-cyclopropylethyl]pyrimidine-5- sulfonamide
208 2-[3-cyano-6-(difluoromethoxy)-1-propyl-1H-indol-2-yl]- 152-154
476.1 N-[(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide 209
2-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol- 183-185
502.0 2-yl]-N-[(1S)-1-cyclopropylethyl]pyrimidine-5- sulfonamide
210 6-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N- 211-216
450.8 [(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 211
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)- 178-181
503.0 N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide
212 6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N- 192-196
489.0 [(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 213
6-(3-cyano-1-cyclohexyl-6-methyl-1H-indol-2-yl)-N- 208-212 491.1
[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 214
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N- 176-182 477.0
[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 215
6-(3-cyano-1-cyclobutyl-6-fluoro-1H-indol-2-yl)-N-[(2R)- 178-180
467.0- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 216
6-[3-cyano-1-(cyclopropylmethyl)-6-fluoro-1H-indol-2- 173-175 466.9
yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide 217
6-(3-cyano-6-fluoro-1-propyl-1H-indol-2-yl)-N-[(2R)- 195-197 455.0
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 218
6-(3-cyano-1-cyclopentyl-6-fluoro-1H-indol-2-yl)-N- 141-144 481.2
[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 219
6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[(2R)- 109-110
467.2- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 220
6-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N- 158-160 481.0
[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 222
6-(6-chloro-3-cyano-1-cyclobutyl-1H-indol-2-yl)-N-[(2R)- 202-206
483.0- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 223
6-(6-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N- N/A 497.0
[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 224
6-(5-chloro-3-cyano-1-cyclopentyl-1H-indol-2-yl)-N- N/A 497.0
[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 236
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N- 170-176
461.1 [(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 237
6-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2- N/A 435.1
yl]-N-[(1S)-1-cyclopropylethyl]pyridine-3-sulfonamide 238
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(1S)- 181-187
435.1- 1-cyclopropylethyl]pyridine-3-sulfonamide 250
6-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-[(1S)- 161-163
467.0- 1-cyclopropylethyl]pyridine-3-sulfonamide 252
6-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-[(2R)- 188-189
465.0- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 254
2-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)- 185-189
476.1 N-[(1S)-1-cyclopropylethyl]pyrimidine-5-sulfonamide 261
6-(3-cyano-1-cyclohexyl-5-fluoro-1H-indol-2-yl)-N-[(2R)- 208-210
494.9- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 262
6-(3-cyano-1-cyclohexyl-6-fluoro-1H-indol-2-yl)-N-[(1S)- 161-162
467.0- 1-cyclopropylethyl]pyridine-3-sulfonamide 263
6-(3-cyano-1,6-dicyclobutyl-1H-indol-2-yl)-N-[(1S)-1- 124-126 475.0
cyclopropylethyl]pyridine-3-sulfonamide 313
6-(3-cyano-1-cyclopentyl-5-methyl-1H-indol-2-yl)-N-[1- 209-214
489.2 (trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide 327
6-(3-cyano-1-cyclopentyl-5-fluoro-1H-indol-2-yl)-N-[1- 202-206
493.2 (trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide 328
6-(3-cyano-1-cyclobutyl-5-methyl-1H-indol-2-yl)-N-[1- 193-199 475.0
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide 329
6-(3-cyano-1-cyclobutyl-5-fluoro-1H-indol-2-yl)-N-[1- 176-183 479.3
(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide 351
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[(2S)- 203-208
463.2- 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 352
6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N- 176-180 477.0
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 353
6-[3-cyano-1-(cyclopropylmethyl)-6-methyl-1H-indol-2- 165-168 463.2
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide 354
6-(3-cyano-1-cyclohexyl-6-methyl-1H-indol-2-yl)-N- 207-212 491.2
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 355
6-[3-cyano-6-methyl-1-(propan-2-yl)-1H-indol-2-yl]-N- 211-216 450.9
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 369
6-(3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-yl)-N- 191-197
489.1 [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 370
6-[3-cyano-1-cyclobutyl-6-(trifluoromethoxy)-1H-indol-2- 165-175
533.0- yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 371 6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-N-
202-211 491.1 (1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-
sulfonamide 382
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol- 170-174
543.1 2-yl]-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-
sulfonamide 383
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-1H-indol-2-yl)- 178-181
503.2 N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide
421 6-(3-cyano-1-cyclobutyl-7-fluoro-6-methyl-1H-indol-2- 210-220
481.2 yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 422
6-(3-cyano-1-cyclobutyl-7-fluoro-6-methyl-1H-indol-2- 186-201 463.2
yl)-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 423
6-(3-cyano-1-cyclopentyl-7-fluoro-6-methyl-1H-indol-2- 211-216
477.3 yl)-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 424
6-(3-cyano-1-cyclopentyl-7-fluoro-6-methyl-1H-indol-2- 191-195
495.3 yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 481
6-(3-cyano-1-cyclobutyl-6-ethyl-1H-indol-2-yl)-N-(1,1,1- 160-165
491.0- trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide 482
6-(3-cyano-1-cyclopentyl-6-fluoro-5-methyl-1H-indol-2- 207-211
477.0 yl)-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 483
6-(3-cyano-1-cyclopentyl-6-fluoro-5-methyl-1H-indol-2- 219-223
495.3 yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 492
6-(3-cyano-1-cyclobutyl-6-fluoro-5-methyl-1H-indol-2- 185-190 481.2
yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide 493
6-(3-cyano-1-cyclobutyl-6-fluoro-5-methyl-1H-indol-2- 209-213 463.2
yl)-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 508
6-(3-cyano-1-cyclopentyl-5,7-difluoro-6-methyl-1H-indol- 215-219
513.2- 2-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 509
6-(3-cyano-1-cyclopentyl-5,7-difluoro-6-methyl-1H-indol- 199-203
495.2- 2-yl)-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 532
6-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol- 186-191
499.2 2-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 533
6-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol- 158-170
481.2 2-yl)-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 555
6-(3-cyano-1-cyclobutyl-4,6-difluoro-5-methyl-1H-indol- 181-186
499.2 2-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 556
6-(3-cyano-1-cyclobutyl-4,6-difluoro-5-methyl-1H-indol- 207-212
481.2 2-yl)-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 557
2-(3-cyano-1-cyclobutyl-7-fluoro-6-methyl-1H-indol-2- 191-198 464.0
yl)-N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 558
6-(3-cyano-1-cyclopentyl-4,6-difluoro-5-methyl-1H-indol- 214-219
495.2- 2-yl)-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 559
6-(3-cyano-1-cyclopentyl-4,6-difluoro-5-methyl-1H-indol- 218-224
513.1- 2-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 577
6-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol- 180-187
513.4 2-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-
sulfonamide 578
6-(3-cyano-1-cyclobutyl-7-fluoro-6-methyl-1H-indol-2- 168-175 495.1
yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3- sulfonamide
579 6-(3-cyano-1-cyclopentyl-7-fluoro-6-methyl-1H-indol-2- 203-205
509.1 yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-
sulfonamide 580
6-(3-cyano-1-cyclopentyl-5,7-difluoro-6-methyl-1H-indol- 226-232
527.3- 2-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-
sulfonamide 586
2-(3-cyano-1-cyclopentyl-7-fluoro-6-methyl-1H-indol-2- 226-232
478.2 yl)-N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 587
6-(3-cyano-1-cyclobutyl-6-methyl-1H-indol-2-yl)-N-[1- 228-232 489.1
(trifluoromethyl)cyclobutyl]pyridine-3-sulfonamide 588
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol- 172-176
555.3 2-yl]-N-[1-(trifluoromethyl)cyclobutyl]pyridine-3-
sulfonamide 589
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-1H-indol- 188-194
529.3 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 613
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2- 223-232
493.2
yl)-N-[1-(trifluoromethyl)cyclopropyl]pyridine-3- sulfonamide 614
6-(3-cyano-1-cyclopentyl-4-fluoro-5-methyl-1H-indol-2- 200-205
509.2 yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-
sulfonamide 615
6-(3-cyano-1-cyclopentyl-4-fluoro-5-methyl-1H-indol-2- 186-197
495.1 yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 625
6-(3-cyano-1-cyclopentyl-4-fluoro-6-methyl-1H-indol-2- 207-211
495.4 yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 626
6-(3-cyano-1-cyclopentyl-4-fluoro-6-methyl-1H-indol-2- 218-223
509.3 yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-
sulfonamide 627
6-(3-cyano-1-cyclobutyl-4-fluoro-6-methyl-1H-indol-2- 205-210 481.4
yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide 628
6-(3-cyano-1-cyclopentyl-4-fluoro-6-methyl-1H-indol-2- 242-246
507.1 yl)-N-[1-(trifluoromethyl)cyclopropyl]pyridine-3- sulfonamide
629 6-(3-cyano-1-cyclobutyl-4-fluoro-6-methyl-1H-indol-2- 241-246
493.1 yl)-N-[1-(trifluoromethyl)cyclopropyl]pyridine-3- sulfonamide
653 6-(3-cyano-1-cyclopentyl-5,7-difluoro-6-methyl-1H-indol-
212-217 513.2- 2-yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 654
6-(3-cyano-1-cyclopentyl-5,7-difluoro-6-methyl-1H-indol- 241-246
525.2- 2-yl)-N-[1-(trifluoromethyl)cyclopropyl]pyridine-3-
sulfonamide 655
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2- 222-226 427.2
yl)-N-(propan-2-yl)pyridine-3-sulfonamide 656
2-(3-cyano-1-cyclopentyl-5,7-difluoro-6-methyl-1H-indol- 230-234
496.0- 2-yl)-N-(1,3-difluoropropan-2-yl)pyrimidine-5- sulfonamide
666 6-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol- 185-190
499.0 2-yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 667
6-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol- 235-241
510.8 2-yl)-N-[1-(trifluoromethyl)cyclopropyl]pyridine-3-
sulfonamide 668
2-(3-cyano-1-cyclobutyl-5,7-difluoro-6-methyl-1H-indol- N/A 481.9
2-yl)-N-(1,3-difluoropropan-2-yl)pyrimidine-5- sulfonamide
Example 5
6-[3-cyano-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-difluoropropan--
2-yl)pyridine-3-sulfonamide (Cpd 96)
##STR00227##
Step A: A solution of 5-fluoroindole (4.03 g, 29.82 mmol) in DMF
(30 ml) was cooled to -30.degree. C. and treated with
chlorosulfonyl isocyanate (6.33 g, 44.73 mmol). After the addition
the reaction mixture was stirred at 0.degree. C. for 3 h. The
reaction mixture was poured into ice water (350 mL) and solid was
collected by filtration, washed with water and dried to afford a
light-yellow solid (4.58 g, 96% yield).
##STR00228##
Step B: To a solution of 5-fluoro-1H-indole-3-carbonitrile (500 mg,
3.1 mmol) in DMF (10 mL) was added 2-fluoropyridine (390 mg, 4.1
mmol) and cesium carbonate (2.1 g, 6.2 mmol). The mixture was
heated at 90.degree. C. for 16 hours, cooled to room temperature
and poured into water (200 mL). After stirring for 1 hour a
precipitate was collected and washed with water (200 mL) and hexane
(200 mL). The solid was dried under vacuum to provide a light
yellow powder (650 mg, 88%). .sup.1H NMR (CDCl.sub.3, 500 MHz):
.delta. 8.65 (1H, m), 8.24 (1H, s), 8.15 (1H, m), 7.95 (1H, m),
7.50 (2H, m), 7.36 (1H, m), 7.17 (1H, m).
##STR00229##
Step C: To a solution of
5-fluoro-1-(pyridin-2-yl)-1H-indole-3-carbonitrile (490 mg, 2.1
mmol) in THF (10 mL) at 0.degree. C. was added tributyltin iodide
(1.56 g, 3.7 mmol) followed by LDA (2.1 mL, 3.1 mmol). The mixture
was stirred at 0.degree. C. for 30 minutes, quenched with sat. aq.
ammonium chloride (10 mL) and extracted with ethyl acetate (100
mL). The organic layer was filtered through a short layer of silica
gel and celite and concentrated to provide a light-yellow oil (0.8
g, 75%).
##STR00230##
Step D: To a solution of
5-fluoro-1-(pyridin-2-yl)-2-(tributylstannyl)-1H-indole-3-carbonitrile
(200 mg, 0.37 mmol) in dioxane (0.6 mL) was added
6-chloro-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide (65 mg,
0.24 mmol), palladium tetrakis-triphenylphosphine (29 mg, 0.024
mmol), and copper (I) iodide (4 mg, 0.048 mmol). The mixture was
purged with argon, heated to 95.degree. C. and stirred for 16
hours. The mixture was cooled to room temperature, filtered through
a layer of celite, then condensed and purified by flash
chromatography to provide the title Compound 96 as a light yellow
powder (49 mg, 42%) was obtained. Melting point: 170-172; MS m/z
472.0 M+H.sup.+; .sup.1H NMR (CDCl.sub.3, 500 MHz): .delta. 8.75
(1H, d, J=1.9 Hz), 8.43 (1H, dd, J=1.3 Hz, 4.9 Hz), 8.17 (1H, dd,
J=2.4 Hz, 8.4 Hz), 7.97 (1H, d, J=8.4 Hz), 7.83 (1H, m), 7.40 (1H,
m), 7.34 (3H, m), 7.08 (1H, m), 5.06 (1H, d, J=9.0 Hz), 4.38 (4H,
m), 3.78 (1H, m).
Additional compounds representative of the present invention may be
prepared according to the procedure of Example 5 by substituting
the appropriate starting materials, reagents and reaction
conditions and include compounds selected from (wherein MS
represents mass spec as MH.sup.+, unless otherwise indicated, m.p.
represents melting point in .degree. C., and N/A indicates that the
data was not obtained):
TABLE-US-00009 Cpd Name m.p. MS 95
6-(3-cyano-6-cyclopropyl-1-phenyl-1H-indol-2-yl)-N-(1,3- 171-175
493.0 difluoropropan-2-yl)pyridine-3-sulfonamide 111
6-(3-cyano-6-methyl-1-phenyl-1H-indol-2-yl)-N-(1,3- 181-185 466.9
difluoropropan-2-yl)pyridine-3-sulfonamide 112
6-(5-chloro-3-cyano-1-phenyl-1H-indol-2-yl)-N-(1,3- 192-196 486.9
difluoropropan-2-yl)pyridine-3-sulfonamide 113
6-(3-cyano-5-fluoro-1-phenyl-1H-indol-2-yl)-N-(1,3- 165-168 471.1
difluoropropan-2-yl)pyridine-3-sulfonamide 226
6-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]-N- 200-202
519.- 0 (1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 227
6-[3-cyano-6-(difluoromethoxy)-1-(2-fluorophenyl)-1H- 188-191 537.0
indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3- sulfonamide 228
6-[3-cyano-6-(difluoromethoxy)-1-(4-fluorophenyl)-1H- 192-198 537.1
indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3- sulfonamide 248
6-[3-cyano-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3- 159-162
46- 8.0 difluoropropan-2-yl)pyridine-3-sulfonamide 249
6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indol-2- 186-190
51- 9.8 yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 259
6-[3-cyano-5-fluoro-1-(pyridin-4-yl)-1H-indol-2-yl]-N-(1,3- 199-203
47- 2.0 difluoropropan-2-yl)pyridine-3-sulfonamide 260
2-(3-cyano-6-methyl-1-phenyl-1H-indol-2-yl)-N-(1,3- 169-171 468.1
difluoropropan-2-yl)pyrimidine-5-sulfonamide 336
6-[3-cyano-5-fluoro-1-(4-methoxyphenyl)-1H-indol-2-yl]-N- 198-200
501.- 0 (1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 337
2-[3-cyano-5-fluoro-1-(4-methoxyphenyl)-1H-indol-2-yl]-N- 209-211
502.- 2 (1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 356
6-[3-cyano-5-fluoro-1-(4-methylphenyl)-1H-indol-2-yl]-N- 208-210
485.8- (1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 357
2-[3-cyano-5-fluoro-1-(4-methylphenyl)-1H-indol-2-yl]-N- 200-202
450.1- (propan-2-yl)pyrimidine-5-sulfonamide 368
6-[3-cyano-6-(difluoromethoxy)-1-(4-fluorophenyl)-1H- 195-198 550.0
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 386
6-[3-cyano-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-
210-212 4- 90.0 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
387 6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indol-2-
199-203 53- 8.0 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 437
6-[6-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-
177-178 5- 06.1 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
438 6-[6-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-
219-221 48- 8.1 difluoropropan-2-yl)pyridine-3-sulfonamide 439
6-[3-cyano-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N- 208-210
437.0 (propan-2-yl)pyridine-3-sulfonamide 440
6-(3-cyano-6-methyl-1-phenyl-1H-indol-2-yl)-N-[(2S)-1,1,1- 196-198
465- .2 trifluoropropan-2-yl]pyridine-3-sulfonamide 441
6-(5-chloro-3-cyano-1-phenyl-1H-indol-2-yl)-N-[(2S)-1,1,1- 210-212
505- .3 trifluoropropan-2-yl]pyridine-3-sulfonamide 442
6-[5-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-
186-188 5- 06.2 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
443 6-[5-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-
187-188 48- 7.8 difluoropropan-2-yl)pyridine-3-sulfonamide 449
2-[6-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-
163-166 5- 07.1 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide
450 2-[6-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-
234-235 49- 0.9 difluoropropan-2-yl)pyrimidine-5-sulfonamide 474
2-[3-cyano-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-
209-210 4- 91.3 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide
475 2-[3-cyano-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-
210-212 4- 87.2 1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide
476 6-[3-cyano-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-
199-203 4- 86.2 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
477 2-[3-cyano-6-(difluoromethoxy)-1-(4-fluorophenyl)-1H- 213-216
538.2 indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5-
sulfonamide 488
6-[6-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(1S)-
199-201 4- 77.9 1-cyclopropylethyl]pyridine-3-sulfonamide 489
6-[6-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2R)-
198-199 5- 06.2 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
490 6-[5-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(1S)-
136-139 4- 77.9 1-cyclopropylethyl]pyridine-3-sulfonamide 491
6-[5-chloro-3-cyano-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2R)-
150-154 5- 06.3 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
501 6-[3-cyano-6-cyclopropyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-
210-213 49- 4.3 (1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 502
6-[3-cyano-6-cyclopropyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N- 185-189
51- 2.3 [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 503
6-[3-cyano-5-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2S)-
165-167 4- 86.3 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
504 6-[3-cyano-5-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-(1,3-
177-179 46- 8.2 difluoropropan-2-yl)pyridine-3-sulfonamide 512
6-[3-cyano-6-(difluoromethoxy)-1-(pyrimidin-2-yl)-1H-indol- 186-189
53- 9.3 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 534
6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indol-2- 159-161
53- 8.2 yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 540
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-
233-236 - 486.2 N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide
553 6-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]-N-
209-211 537.- 1
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 554
6-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]-N- 212-213
537.- 2 [(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 583
6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indol-2- 170-173
55- 3.2 yl]-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-
sulfonamide 584
6-[3-cyano-6-cyclopropyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N- N/A
526.3 (1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide
585 6-(3-cyano-6-methyl-1-phenyl-1H-indol-2-yl)-N-(1,1,1- 210-212
499.2 trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide 602
6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N- 231-234
505.1- (1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide
608 6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-(1,3-
N/A 473.- 0 difluoropropan-2-yl)pyridine-3-sulfonamide 610
2-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]-N- 206-208
520.- 2 (1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 611
2-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]-N- 216-218
538.- 2 [(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5-sulfonamide
612 6-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-indol-2-yl]-N-
218-220 551.- 3
(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide 623
6-[3-cyano-6-(difluoromethoxy)-1-(pyridin-2-yl)-1H-indol-2- N/A
550.8 yl]-N-[1-(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide
624 N-tert-butyl-6-[3-cyano-6-(difluoromethoxy)-1-phenyl-1H-
216-218 497.2- indol-2-yl]pyridine-3-sulfonamide 635
6-[3-cyano-6-(difluoromethoxy)-1-(pyrimidin-2-yl)-1H-indol- 173-176
52- 1.8 2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 649
6-[3-cyano-6-(difluoromethoxy)-1-(4-fluorophenyl)-1H- 199-203 555.0
indol-2-yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 657
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(pyridine-2-yl)- 161-163
556- .0
1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 663
6-[3-cyano-6-(difluoromethoxy)-1-(pyrimidin-2-yl)-1H-indol- 179-180
55- 2.9 2-yl]-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-
sulfonamide 664
6-[3-cyano-6-(difluoromethoxy)-1-(4-fluorophenyl)-1H- 195-198 567.2
indol-2-yl]-N-[1-(trifluoromethyl)cyclopropyl]pyridine-3-
sulfonamide 670
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(pyridin-2-yl)- 179-180
552.- 9
1H-indol-2-yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 671
6-[3-cyano-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N-[(2R)-
195-198 5- 67.2 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
672 6-(3-cyano-1-cyclopentyl-6-ethyl-5-fluoro-1H-indol-2-yl)-N-
142-143 52- 3.2
(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide 673
6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N- 202-205
490.8- [(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 677
6-[3-cyano-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N- 195-198
487.2- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 686
6-[3-cyano-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-N- 208-209
499.9 (1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide
687 6-[3-cyano-6-(difluoromethoxy)-1-(4-fluorophenyl)-1H- 215-216
569.2 indol-2-yl]-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-
3-sulfonamide 688
6-[3-cyano-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N- 196-198
487.0- [(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 689
6-[3-cyano-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N- 202-205
501.2- (1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-sulfonamide
690 6-[3-cyano-6-(difluoromethoxy)-1-(pyrimidin-2-yl)-1H-indol-
170-174 55- 0.8 2-yl]-N-[1-(trifluoromethyl)cyclopropyl]pyridine-3-
sulfonamide 695
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2-yl)-1H-indol-2- N/A
505.2 yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 698
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)-1H-indol-2-yl]-
170-174 - 504.1
N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
Example 6
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-tr-
ifluoropropan-2-yl]pyridine-3-sulfonamide (Cpd 409)
##STR00231##
Step A: A 2 L dry round bottom flask was charged with
1-bromo-2-fluoro-4-methyl-5-nitrobenzene (24.5 g, 0.1 mol, 97%),
DMF-DIPA (39 g, 0.22 mol), Et.sub.3N (16 mL, 0.11 mol) and dry DMF
(100 mL). The mixture was stirred at 130.degree. C. for 2 h. After
removal of the volatiles the residue was dissolved in a mixture of
toluene (650 mL) and acetic acid (390 mL) followed by addition of
iron powder (55 g) and silica gel (50 g). The dark red mixture was
heated to 100.degree. C. with vigorous stirring. The dark color
disappeared after refluxing for 20 min indicating completion of
reaction. The mixture was then cooled to 25.degree. C., diluted
with EtOAc and filtered. The cake was washed thoroughly with EtOAc.
The combined filtrates were washed with sat. aq.
Na.sub.2S.sub.2O.sub.5, sat. aq. NaHCO.sub.3, and brine, dried over
Na.sub.2SO.sub.4 and concentrated. The residue was purified on a
silica gel column eluting with 5/1 hexanes/CH.sub.2Cl.sub.2 to
provide 6-bromo-5-fluoro-1H-indole as a white crystalline solid
(16.2 g, 76%).
##STR00232##
Step B: To 6-bromo-5-fluoro-1H-indole (9.4 g, 43.9 mmol) in DMF (50
mL) at -78.degree. C. was added chlorosulfonyl isocyanate (4.6 mL,
53 mmol). After complete addition the mixture was allowed to warm
to room temperature and stir for 2 hrs. The reaction mixture was
poured into ice water and stirred for 30 minutes. The precipitate
was collected on a filter, washed with ice water and dried in a
vacuum oven to give 6-bromo-5-fluoro-1H-indole-3-carbonitrile as a
light-beige solid (10.5 g, 100%).
##STR00233##
Step C: To the 6-bromo-5-fluoro-1H-indole-3-carbonitrile (10.5 g,
43.9 mmol) was added cesium carbonate (30 g, 92.2 mmol), DMF (80
mL), and then cyclopentylbromide (6.2 mL, 65.8 mmol). This mixture
was stirred at 88.degree. C. for 40 h, cooled to room temperature
and then poured into ice water. The precipitate was collected,
washed with water and dried to give
6-bromo-1-cyclopentyl-5-fluoro-1H-indole-3-carbonitrite as a light
grey solid (12.6 g, 93%).
##STR00234##
Step D: Into a solution of
6-bromo-1-cyclopentyl-5-fluoro-1H-indole-3-carbonitrile (6.6 g,
21.5 mmol) and PdCl.sub.2dppf (0.31 g, 0.43 mmol) in dioxane (45
mL) was added a solution of dimethylzinc in toluene (1.2 M, 35.8
mL, 43 mmol). The atmosphere was replaced with nitrogen. The
mixture was stirred at 90.degree. C. for 90 min and then cooled to
room temperature. The reaction was quenched by careful addition of
methanol. Ethyl acetate (200 mL) was added and the mixture washed
with aq. 2 N HCl, water and brine, dried over Na.sub.2SO.sub.4 and
concentrated. The residue was purified on silica gel eluting with a
gradient of 5 to 35% ethyl acetate in hexane to provide
1-cyclopentyl-5-fluoro-6-methyl-1H-indole-3-carbonitrile (4.4 g,
85%)
##STR00235##
Step E: Into a solution of
1-cyclopentyl-5-fluoro-6-methyl-1H-indole-3-carbonitrile (4.4 g,
18.2 mmol) and triisopropyl borate (7.6 mL, 33 mmol) in THF (75 mL)
at -78.degree. C. was added LDA (1.5 M in cyclohexane, 15.8 mL,
23.7 mmol). The mixture was stirred at -78.degree. C. for 30 min,
quenched with ice water (200 mL) and stirred for 15 min without
cooling. The mixture was extracted with ethyl acetate 1:1 in hexane
(20 mL). The aqueous layer was acidified with aq. 2 N HCl to pH 5
and then extracted with CH.sub.2Cl.sub.2 (100 mL). The organic
layer was dried over Na.sub.2SO.sub.4 and concentrated to give
3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-ylboronic acid as a
solid (6.2 g, 90% pure by LCMS) which was used in the next step
without further purification.
##STR00236##
Step F: A mixture of
3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-ylboronic acid
prepared as above (6.0 g, 18.8 mmol, 90%),
(R)-6-chloro-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide
(3.63 g, 12.5 mmol) (similarly prepared as described in Example 4,
Step A), tri-tert-butylphosphonium tetrafluoroborate (0.36 g, 1.2
mmol), Pd.sub.2(dba).sub.3 (0.57 g, 0.62 mmol) and potassium
fluoride (7.25 g, 125 mmol) in THF (80 mL) was stirred at
40.degree. C. overnight. The solvent was then evaporated and the
residue purified on silica gel eluting with a gradient of 0 to 10%
ethyl acetate in CH.sub.2Cl.sub.2 to provide
(R)-6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-(-
1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (5.83 g, 94%).
Melting point: 191-193.degree. C.; MS m/z 495.0 M+H.sup.+; .sup.1H
NMR (500 MHz, CDCl.sub.3): .delta. 9.24 (1H, t, J=1.1 Hz), 8.34
(1H, dd, J=8.3 Hz, J=2.4 Hz), 8.05 (1H, dd, J=8.3, 0.7 Hz), 7.43
(1H, d, J=9.2 Hz), 7.37 (1H, d, J=6.0 Hz), 5.26-5.19 (2H, m),
4.20-4.12 (1H, m), 2.46 (3H, d, J=1.9 Hz), 2.31-2.26 (2H, m),
2.20-2.16 (2H, m), 2.07-2.04 (2H, m), 1.80-1.76 (2H, m), 1.45 (3H,
d, J=7.0 Hz).
Additional compounds representative of the present invention may be
prepared according to the procedure of Example 6 by substituting
the appropriate starting materials, reagents and reaction
conditions and include compounds selected from (wherein MS
represents mass spec as MH.sup.+, unless otherwise indicated, m.p.
represents melting point in .degree. C., and N/A indicates that the
data was not obtained):
TABLE-US-00010 Cpd Name m.p. MS 340
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2- 218-219 481.0
yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide 407
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2- 211-213
477.1 yl)-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 408
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2- 168-171
495.0 yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 539
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2- 238-243 495.3
yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3- sulfonamide
609 6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2- 211-214
481.3 yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 630 6-(3-cyano-1-cyclobutyl-6-cyclopropyl-5-fluoro-1H-
201-203 507.1
indol-2-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 631 6-(3-cyano-1-cyclobutyl-6-cyclopropyl-5-fluoro-1H-
190-194 507.1
indol-2-yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 632
6-(3-cyano-1-cyclopentyl-6-ethyl-5-fluoro-1H-indol-2- 205.5-206
509.2 yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 633
6-(3-cyano-1-cyclopentyl-6-ethyl-5-fluoro-1H-indol-2- 201-202 509.2
yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide 637
6-(3-cyano-1-cyclopentyl-6-ethyl-5-fluoro-1H-indol-2- 198-199 521.2
yl)-N-[1-(trifluoromethyl)cyclopropyl]pyridine-3- sulfonamide 638
2-(3-cyano-1-cyclopentyl-6-ethyl-5-fluoro-1H-indol-2- 184-185 492.2
yl)-N-(1,3-difluoropropan-2-yl)pyrimidine-5-sulfonamide 639
6-(3-cyano-1-cyclopentyl-6-ethyl-5-fluoro-1H-indol-2- 179.5-180.0
491.- 2 yl)-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 640
6-(3-cyano-1-cyclobutyl-6-ethyl-5-fluoro-1H-indol-2-yl)- 205-206
495.2- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide
641 6-(3-cyano-1-cyclobutyl-6-ethyl-5-fluoro-1H-indol-2-yl)-
199-199.5 495.2 N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 642
6-(3-cyano-1-cyclobutyl-6-ethyl-5-fluoro-1H-indol-2-yl)- 203-203.5
507.2 N-[1-(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide 643
N-tert-butyl-6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl- 208-209
455.2- 1H-indol-2-yl)pyridine-3-sulfonamide 644
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2- N/A 507.7
yl)-N-[1-(trifluoromethyl)cyclopropyl]pyridine-3- sulfonamide 645
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2- 208-209
453.2 yl)-N-(1-methylcyclopropyl)pyridine-3-sulfonamide 651
N-tert-butyl-6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl- 223-228
441.2 1H-indol-2-yl)pyridine-3-sulfonamide 652
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2- N/A 425.2
yl)-N-cyclopropylpyridine-3-sulfonamide 661
6-(3-cyano-1-cyclopentyl-6-cyclopropyl-5-fluoro-1H- 189-190 521.3
indol-2-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 662 6-(3-cyano-1-cyclopentyl-6-cyclopropyl-5-fluoro-1H-
180-181 521.2
indol-2-yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 665
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-methyl- N/A 529.2
1H-indol-2-yl]-N-[(2R)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 678
6-(3-cyano-1-cyclohexyl-5-fluoro-6-methyl-1H-indol-2- 224-229 509.2
yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide 679
2-(3-cyano-1-cyclohexyl-5-fluoro-6-methyl-1H-indol-2- N/A 510.2
yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrimidine-5- sulfonamide
680 6-(3-cyano-1-cyclohexyl-5-fluoro-6-methyl-1H-indol-2- 224-229
509.3 yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 681
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2- 223-225
509.2 yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-
sulfonamide 697
6-[3-cyano-1-cyclobutyl-6-(2,2-difluoroethyl)-5-fluoro- N/A 531.2
1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 705
6-(3-cyano-1-cyclohexyl-5-fluoro-6-methyl-1H-indol-2- 248-254 523.3
yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3- sulfonamide
709 N-{[6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H- 162-163
536.9 indol-2-yl)pyridin-3-yl]sulfonyl}-N-[(2R)-1,1,1-
trifluoropropan-2-yl]acetamide 710
N-tert-butyl-6-(3-cyano-1-cyclohexyl-5-fluoro-6-methyl- 244-245
470.0 1H-indol-2-yl)pyridine-3-sulfonamide 749
6-[3-cyano-5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4- N/A 511.2
yl)-1H-indol-2-yl]-N-[(2R)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 750
6-[3-cyano-5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4- N/A 525.2
yl)-1H-indol-2-yl]-N-(1,1,1-trifluoro-2-methylpropan-2-
yl)pyridine-3-sulfonamide 751
6-[3-cyano-5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4- N/A 511.1
yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 752
N-tert-butyl-6-[3-cyano-5-fluoro-6-methyl-1-(tetrahydro- N/A 471.2
2H-pyran-4-yl)-1H-indol-2-yl]pyridine-3-sulfonamide 753
2-[3-cyano-5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4- N/A 512.2
yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyrimidine-5-sulfonamide 764
N-tert-butyl-6-(3-cyano-1-cyclobutyl-6-ethyl-5-fluoro- 186-188
453.1 1H-indol-2-yl)pyridine-3-sulfonamide 772
6-[3-cyano-1-cyclobutyl-5-fluoro-6-(methylsulfanyl)-1H- 201-203
513.2 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 821
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2- 201-207
509.1 yl)-N-[(2S)-1,1,1-trifluorobutan-2-yl]pyridine-3- sulfonamide
826 6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2- 212-217
495.5 yl)-N-[(2S)-1,1,1-trifluorobutan-2-yl]pyridine-3- sulfonamide
831 6-(3-cyano-1-cyclopentyl-6-cyclopropyl-5-fluoro-1H- 183-185
533.2 indol-2-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-
yl)pyridine-3-sulfonamide 832
N-tert-butyl-6-(3-cyano-1-cyclopentyl-6-cyclopropyl-5- 186-188
479.2 fluoro-1H-indol-2-yl)pyridine-3-sulfonamide 836
N-[6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol- 206-208
510.6 2-yl)pyridin-3-yl]-N'-[(2S)-1,1,1-trifluoropropan-2-
yl]sulfuric diamide 837
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2- 237-242
509.3 yl)-5-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 842
1-cyclopentyl-6-cyclopropyl-5-fluoro-2-(5-{[(2S)-1,1,1- 255-257
537.5 trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 856
6-(3-cyano-1-cyclohexyl-5-fluoro-6-methyl-1H-indol-2- N/A 521.2
yl)-N-[1-(trifluoromethyl)cyclopropyl]pyridine-3- sulfonamide 858
6-(3-cyano-1-cyclobutyl-6-ethyl-4-methoxy-1H-indol-2- 187-188 505.1
yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide 868
6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2- 206-211
509.3 yl)-2-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 910
6-(3-cyano-1-cyclopropyl-6-ethyl-5-fluoro-1H-indol-2- N/A 481.1
yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide
Example 7
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl]-N-[(2S-
)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide (Cpd 549)
##STR00237##
Step A: To 6-bromo-5-fluoro-1H-indole-3-carbonitrile (49.2 g, 206
mmol) [prepared as in Example 6, Step B] was added cesium carbonate
(133 g, 408 mmol), DMF (200 mL), and cyclobutylbromide (30 mL, 311
mmol). This mixture was stirred at 90.degree. C. for three days,
cooled to room temperature and poured into ice water. The
precipitate was collected, washed with water and dried to give
6-bromo-1-cyclobutyl-5-fluoro-1H-indole-3-carbonitrile as a light
grey solid (55 g, 90%).
##STR00238##
Step B: A mixture of
6-bromo-1-cyclobutyl-5-fluoro-1H-indole-3-carbonitrile (29.9 g, 102
mmol), bis(pinacolato)diboron (33.7 g, 133 mmol),
PdCl.sub.2dppf-CH.sub.2Cl.sub.2 complex (4.16 g, 5.1 mmol) and
potassium acetate (30 g, 306 mmol) in dioxane (300 mL) was stirred
at 80.degree. C. overnight. The mixture was then cooled to room
temperature, treated with ethyl acetate (200 mL) and filtered
through a silica-celite pad. The filtrate was concentrated,
dissolved in acetone (300 mL) and cooled to 0.degree. C. Into this
solution was added a slurry of Oxone (125.5 g, 204 mmol) in water
(300 mL). The mixture was stirred at room temperature for 15 min,
diluted with ethyl acetate and separated. The aqueous layer was
extracted with ethyl acetate. The organic extractions were combined
and washed with sat. aq. NaHSO.sub.3, and brine, dried over
Na.sub.2SO.sub.4 and concentrated. The residue was purified on
silica gel to provide
1-cyclobutyl-5-fluoro-6-hydroxy-1H-indole-3-carbonitrile as a light
grey solid (19.2 g, 82%).
##STR00239##
Step C: Into a solution of
1-cyclobutyl-5-fluoro-6-hydroxy-1H-indole-3-carbonitrile (1.11 g,
4.83 mmol) in dioxane (10 mL) was added 25% aqueous NaOH (2.5 mL,
16 mmol). Chlorodifluoromethane gas was bubbled through the mixture
at 80.degree. C. for 3 h. The mixture was diluted with water (20
mL) and extracted with ethyl acetate, dried over Na.sub.2SO.sub.4
and concentrated. The residue was purified on silica gel eluting
with a gradient of 5 to 35% ethyl acetate in hexane to give
1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indole-3-carbonitrile
(1.1 g, 82%).
##STR00240##
Step D: Into a solution of
1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indole-3-carbonitrile
(0.83 g, 2.96 mmol) and trimethyl borate (0.5 mL, 4.44 mmol) in THF
(12 mL) at -78.degree. C. was added LDA (1.5 M in cyclohexane, 2.6
mL, 3.85 mmol). The mixture was stirred at -78.degree. C. for 45
min then quenched with 1 N HCl (3.85 mL, 3.85 mmol). Organic
volatiles were evaporated and the mixture was treated with
dichloromethane (30 mL) and water (15 mL) which was acidified to pH
.about.5. The organic layer was dried over Na.sub.2SO.sub.4 and
evaporated to give a residue (0.94 g, .about.50% desired boronic
acid by LC/MS), which was used in the next step without further
purification.
##STR00241##
Step E: Into a mixture of the crude boronic acid from step D (0.30
g, .about.40% purity, 0.37 mmol),
(S)-6-chloro-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide
(0.076 g, 0.26 mmol) and PdCl.sub.2dppf (0.02 g, 0.027 mmol) in
acetonitrile (2.0 mL) was added an aqueous solution of
K.sub.2CO.sub.3 (2.0 M, 0.55 mL, 1.1 mmol). The mixture was stirred
at room temperature over a period of three days. Aqueous workup
followed by flash chromatography with dichloromethane and
ethylacetate (0 to 10%) provided the title compound (0.063 g, 45%).
Melting point: 172-175.degree. C.; MS m/z 533.2 M+H.sup.+; .sup.1H
NMR (500 MHz, CDCl.sub.3): .delta. 9.23 (1H, d, J=2.0 Hz), 8.35
(1H, dd, J=8.5 Hz, J=2.5 Hz), 8.02 (1H, d, J=8.5 Hz), 7.60 (1H, d,
J=2.0 Hz), 7.58 (1H, d, J=6.0 Hz), 6.64 (1H, t, J=73.5 Hz),
5.37-5.30 (1H, m), 4.99 (1H, d, J=9.5 Hz), 4.19-4.13 (1H, m),
2.54-2.40 (4H, m), 1.94-1.86 (2H, m), 1.47 (3H, d, J=7.0 Hz).
Additional compounds representative of the present invention may be
prepared according to the procedure of Example 7 by substituting
the appropriate starting materials, reagents and reaction
conditions and include compounds selected from (wherein MS
represents mass spec as MH.sup.+, unless otherwise indicated, m.p.
represents melting point in .degree. C., and N/A indicates that the
data was not obtained):
TABLE-US-00011 Cpd Name m. p. MS 542
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H- 160-164
515.2- indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-
sulfonamide 573
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-1H- 190-194
529.- 2 indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyridine-3-
sulfonamide 574
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-1H- 181-184
547.- 4 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 575
6-(3-cyano-1-cyclopentyl-5-fluoro-6-hydroxy-1H-indol-2- N/A 479.1
yl)-N-(1,3-difluoropropan-2-yl)pyridine-3-sulfonamide 576
6-(3-cyano-1-cyclopentyl-5-fluoro-6-hydroxy-1H-indol-2- 214-216
497.2 yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 648
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H- 173-175
533.2- indol-2-yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 676
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H- 162-165
546.9- indol-2-yl]-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-
3-sulfonamide 691
6-(3-cyano-1-cyclopentyl-5-hydroxy-6-methyl-1H-indol-2- 232-233
493.1 yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 711
6-(3-cyano-1-cyclobutyl-5-fluoro-6-hydroxy-1H-indol-2-yl)- 194-196
483- .9 N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
712 6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H- N/A
583.4 indol-2-yl]-N-(difluoromethyl)-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide 713
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-1H- 197-200
547.- 3 indol-2-yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 719
N-tert-butyl-6-(3-cyano-1-cyclobutyl-5-fluoro-6-hydroxy- 242-245
443.2- 1H-indol-2-yl)pyridine-3-sulfonamide 720
N-tert-butyl-6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5- N/A
493.3 fluoro-1H-indol-2-yl]pyridine-3-sulfonamide 721
N-tert-butyl-6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5- N/A
543.2 fluoro-1H-indol-2-yl]-N-(difluoromethyl)pyridine-3-
sulfonamide 722
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H- 172-175
437.2- indol-2-yl]pyridine-3-sulfonamide 725
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methoxy-1H-indol-2-yl)- N/A
497.3 N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 726
6-(3-cyano-1-cyclobutyl-6-ethoxy-5-fluoro-1H-indol-2-yl)- 193-196
511.- 2 N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
738 6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-
166-173 N/A
indol-2-yl]-N-[(2S)-1,1,1-trifluorobutan-2-yl]pyridine-3-
sulfonamide 733 5-chloro-1-cyclobutyl-6-methyl-2-(5-{[(2S)-1,1,1-
171-173 516.2
trifluoropropan-2-yl]sulfamoyl}pyrimidin-2-yl)-1H-indole-3-
carboxamide 780 6-chloro-1-cyclobutyl-2-[5-(propan-2- 251-253 448.1
ylsulfamoyl)pyrimidin-2-yl]-1H-indole-3-carboxamide 781
1-cyclobutyl-2-[5-(propan-2-ylsulfamoyl)pyrimidin-2-yl]-6- 222-223
498- .1 (trifluoromethoxy)-1H-indole-3-carboxamide 782
1-cyclopentyl-2-[5-(propan-2-ylsulfamoyl)pyrimidin-2-yl]-6- 238-241
51- 2.2 (trifluoromethoxy)-1H-indole-3-carboxamide 784
6-[3-cyano-6-(difluoromethoxy)-4-fluoro-1-(propan-2-yl)- 193-194
519.2-
1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 786
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-propyl-1H-indol- 162-168
521- .2 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 787
6-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-5- 149-153
533.2 fluoro-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 788
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-propyl-1H-indol- 160-166
521- .2 2-yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 789
6-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-5- 148-153
533.2 fluoro-1H-indol-2-yl]-N-[(2R)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 790
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H- N/A 546.5
indol-2-yl]-N-(1,1,1-trifluorobutan-2-yl)pyridine-3- sulfonamide
791 6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-
178-179 513.2- indol-2-yl]-N-phenylpyridine-3-sulfonamide 797
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-4-fluoro-1H- 210-212
531.1- indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 808
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H- 169-171
545.2- indol-2-yl]-N-[1-(trifluoromethyl)cyclopropyl]pyridine-3-
sulfonamide 812
6-[3-cyano-1-(cyclopropylmethyl)-6-(difluoromethoxy)-5- 173-178
437.2 fluoro-1H-indol-2-yl]pyridine-3-sulfonamide 813
6-(3-cyano-1-cyclobutyl-5-fluoro-6-hydroxy-1H-indol-2-yl)- N/A
495.1 N-[1-(trifluoromethyl)cyclopropyl]pyridine-3-sulfonamide 822
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H- 204-210
547.1- indol-2-yl]-4-methyl-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 827
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H- 150-155
547.1- indol-2-yl]-5-methyl-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 862
6-[3-cyano-1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-1H- 185-186
461.- 3
indol-2-yl]-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-
3-sulfonamide 936
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(propan-2-yl)- 184-188
521.0-
1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 937 6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(2-
130-134 535.3
methylpropyl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-
2-yl]pyridine-3-sulfonamide 940
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1-(2- 203-208 523.1
hydroxyethyl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-
2-yl]pyridine-3-sulfonamide 1065
N-{5-[3-cyano-1-cyclohexyl-6-(difluoromethoxy)-5-fluoro- 278-280
521.- 6 1H-indol-2-yl]pyridin-2-yl}-2-methylpropane-2-sulfonamide
1082 N-(5-{3-cyano-1-[(1S)-1-cyclopropylethyl]-6-ethyl-5-fluoro-
215.5-217- .0 496.6
1H-indol-2-yl}pyridin-2-yl)-2-methylpropane-2-sulfonamide 1092
N-[6-(3-cyano-1-cyclohexyl-6-cyclopropyl-4-fluoro-1H- 252-255 495.5
indol-2-yl)pyridin-3-yl]-2-methylpropane-2-sulfonamide 1118
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-cyclobutyl-6-
263-268- 473.3 ethyl-4-fluoro-1H-indole-3-carboxamide
Example 8
6-[3-cyano-6-cyclopropyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide (Cpd 650)
##STR00242##
Step A: To a solution of tert-butyl
6-cyclopropyl-1H-indole-1-carboxylate (1.93 g, 7.51 mmol) and
triisopropylborate (2.58 mL, 11.26 mmol) in THF was added LDA (1.5
M in cyclohexane, 7.0 mL, 10.5 mmol) at -78.degree. C. The mixture
was stirred at -78.degree. C. for 30 min, quenched with ice water
(60 mL) and stirred for 15 min without cooling. The mixture was
extracted with ethyl acetate 1:1 in hexane (20 mL). The aqueous
layer was acidified with aq. 2 N HCl to pH 5 and then extracted
with CH.sub.2Cl.sub.2 (60 mL). The organic layer was dried over
Na.sub.2SO.sub.4 and concentrated to give
1-(tert-butoxycarbonyl)-6-cyclopropyl-1H-indol-2-ylboronic acid as
a solid (2.0 g, 88% yield) that was used in the next step without
further purification.
##STR00243##
Step B: A mixture of
1-(tert-butoxycarbonyl)-6-cyclopropyl-1H-indol-2-ylboronic acid
(1.10 g, 3.64 mmol),
(S)-6-chloro-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide
(1.05 g, 3.64 mmol), PdCl.sub.2(dppf) (178 mg, 0.22 mmol), aq.
K.sub.2CO.sub.3 (2 M, 5.46 mL, 10.9 mmol) in acetonitrile (8 mL)
was stirred at 50.degree. C. overnight. The solvent was then
evaporated and the residue purified on silica gel eluting with 0 to
10% ethyl acetate in CH.sub.2Cl.sub.2 to provide (S)-tert-butyl
6-cyclopropyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)sulfamoyl)pyridin-2-yl)-
-1H-indole-1-carboxylate (1.51 g, 81% yield). MS m/z 510.3
M+H.sup.+; .sup.1H NMR (500 MHz, CDCl.sub.3): .delta. 9.65 (1H, s),
8.50 (1H, m), 8.01 (1H, d, J=8.2 Hz), 7.85 (1H, s), 7.52-7.49 (2H,
m), 6.98 (1H, d, J=8.2 Hz), 4.98 (1H, d, J=8.4 Hz), 4.02 (1H, m),
2.02-1.98 (1H, m), 1.34 (3H, d, J=7.5 Hz), 0.98-0.96 (2H, m),
0.76-0.72 (2H, m).
##STR00244##
Step C: To a solution of (S)-tert-butyl
6-cyclopropyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)sulfamoyl)pyridin-2-yl)-
-1H-indole-1-carboxylate (503 mg, 0.99 mmol) and K.sub.2CO.sub.3
(276 mg, 2 mmol) in DMF (5 mL) was added allyl bromide (0.11 mL,
1.30 mmol). The mixture was stirred at room temperature for 2 hrs,
and quenched with water (60 mL). The mixture was extracted with
CH.sub.2Cl.sub.2 (3.times.20 mL). The solvent was then evaporated
and (S)-tert-butyl
2-(5-(N-allyl-N-(1,1,1-trifluoropropan-2-yl)sulfamoyl)pyridin-2-yl)-6-cyc-
lopropyl-1H-indole-1-carboxylate was obtained as a light yellow oil
(500 mg, 92% yield). MS m/z 550.3 M+H.sup.+. This material was used
in the next step without further purification.
##STR00245##
Step D: To a solution of (S)-tert-butyl
2-(5-(N-allyl-N-(1,1,1-trifluoropropan-2-yl)sulfamoyl)pyridin-2-yl)-6-cyc-
lopropyl-1H-indole-1-carboxylate (500 mg, 0.91 mmol) in
acetonitrile was added pyrrolidine (0.35 mL, 4.55 mmol). The
mixture was stirred at room temperature for 5 hrs and the solvent
was evaporated. The residue was purified on silica gel eluting with
0 to 10% ethyl acetate in CH.sub.2Cl.sub.2 to provide
(S)-N-allyl-6-(6-cyclopropyl-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl-
)pyridine-3-sulfonamide (370 mg, 91% yield). MS m/z 450.2
M+H.sup.+; .sup.1H NMR (500 MHz, CDCl.sub.3): .delta. 9.28 (1H, s),
8.85 (1H, s), 7.96 (1H, d, J=5.5 Hz), 7.74 (1H, d, J=9.5 Hz), 7.49
(1H, d, J=5.5 Hz), 7.09 (1H, s), 7.01 (1H, s), 6.82-6.80 (1H, m),
5.75 (1H, m), 5.16-5.10 (2H, m), 4.64-4.62 (1H, m), 3.89 (2H, d,
J=5.0 Hz), 2.00-1.96 (1H, m), 1.35 (3H, d, J=6.0 Hz), 0.98-0.96
(2H, m), 0.75-0.72 (2H, m).
##STR00246##
Step E: To a solution of
(S)-N-allyl-6-(6-cyclopropyl-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl-
)pyridine-3-sulfonamide sulfonamide (370 mg, 0.82 mmol) in DMF (5
mL) was added chlorosulfonyl isocyanate (0.14 mL, 1.6 mmol) at
-30.degree. C. The mixture was then warmed to 0.degree. C. and
stirred for 2 hrs. The mixture was then quenched with water (60
mL), extracted with CH.sub.2Cl.sub.2 (3.times.20 mL) and washed
with brine (3.times.30 mL). The organic layer was collected, dried
over Na.sub.2SO.sub.4, concentrated and the purified on silica gel
eluting with 0 to 10% ethyl acetate in CH.sub.2Cl.sub.2 to provide
(S)-N-allyl-6-(3-cyano-6-cyclopropyl-1H-indol-2-yl)-N-(1,1,1-trifluoropro-
pan-2-yl)pyridine-3-sulfonamide (186 mg, 50% yield). MS m/z 475.2
M+H.sup.+; .sup.1H NMR (500 MHz, CDCl.sub.3): .delta. 9.80 (1H, s),
9.02 (1H, s), 8.44 (1H, dd, J=1.0, 9.0 Hz), 8.11 (1H, dd, J=2.5,
8.5 Hz), 7.59 (1H, d, J=8.5 Hz), 7.20 (1H, s), 7.00 (1H, d, J=2.5,
8.5 Hz), 5.52 (1H, m), 5.28-5.20 (2H, m), 4.50 (1H, m), 3.98 (1H,
bs), 2.02-1.96 (1H, m), 1.43 (3H, d, J=7.0 Hz), 0.98-0.96 (2H, m),
0.75-0.72 (2H, m).
##STR00247##
Step F: A mixture of
(S)-N-allyl-6-(3-cyano-6-cyclopropyl-1H-indol-2-yl)-N-(1,1,1-trifluoropro-
pan-2-yl)pyridine-3-sulfonamide (140 mg, 0.30 mmol),
2-bromo-pyrimidine (98 mg, 0.59 mmol), copper (I) iodide (11 mg,
0.06 mmol), (1R,2R)-N1,N2-dimethylcyclohexane-1,2-diamine (0.02 mL,
0.12 mmol), and K.sub.3PO.sub.4 (134 mg, 0.60 mmol) in toluene was
stirred at 100.degree. C. for 16 hrs. The mixture was then filtered
through celite and the solvent evaporated. The residue was purified
on silica gel eluting with 0 to 10% ethyl acetate in
CH.sub.2Cl.sub.2 to provide
(S)-N-allyl-6-(3-cyano-6-cyclopropyl-1-(pyrimidin-2-yl)-1H-indol-2-yl)-N--
(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (140 mg, 86%).
MS m/z 553.3 M+H.sup.+; .sup.1H NMR (500 MHz, CDCl.sub.3): .delta.
8.65 (1H, d, J=3.0 Hz), 8.62 (2H, d, J=4.0 Hz), 8.14 (1H, dd,
J=4.0, 8.0 Hz), 8.01 (1H, d, J=9.0 Hz), 7.75 (1H, s), 7.64 (1H, d,
J=7.5 Hz), 7.21-7.19 (1H, m), 7.04 (1H, d, J=9.0 Hz), 5.60 (1H, m),
5.28-5.25 (2H, m), 4.50 (1H, m), 3.86 (1H, d, J=6.5 Hz), 2.02-1.96
(1H, m), 1.32 (3H, d, J=8.5 Hz), 0.98-0.96 (2H, m), 0.75-0.72 (2H,
m).
##STR00248##
Step G: To a solution of
(S)-N-allyl-6-(3-cyano-6-cyclopropyl-1-(pyrimidin-2-yl)-1H-indol-2-yl)-N--
(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (70 mg, 0.13
mmol) and PdCl.sub.2(dppf) (10 mg, 0.013 mmol) in THF (1 mL) was
added NaBH(AcO).sub.3 (40 mg, 0.19 mmol). The mixture was stirred
at room temperature for 16 hrs and CH.sub.2Cl.sub.2 (20 mL) was
added. The mixture was washed with sat. aq. NH.sub.4C1 (20 mL),
concentrated and purified on silica gel eluting with 0 to 10% ethyl
acetate in CH.sub.2Cl.sub.2 to provide
(S)-6-(3-cyano-6-cyclopropyl-1-(pyrimidin-2-yl)-1H-indol-2-yl)-N-(1,1,1-t-
rifluoropropan-2-yl)pyridine-3-sulfonamide (54 mg, 83%). Melting
point: 181-184.degree. C.; MS m/z 513.2 M+H.sup.+; .sup.1H NMR (500
MHz, CDCl.sub.3): .delta.8.28 (1H, s), 8.72 (1H, d, J=2.0 Hz), 8.60
(2H, d, J=9.0 Hz), 8.19 (1H, d, J=2.5 Hz), 8.18 (1H, d, J=2.0 Hz),
8.02 (1H, d, J=9.0 Hz), 7.76 (1H, s), 7.65 (1H, d, J=8.0 Hz),
7.21-7.20 (1H, m), 7.05 (1H, d, J=9.0 Hz), 5.50 (1H, s), 4.02-3.98
(1H, m), 2.02-1.96 (1H, m), 1.31 (3H, d, J=6.0 Hz), 0.98-0.96 (2H,
m), 0.75-0.72 (2H, m).
Additional compounds representative of the present invention may be
prepared according to the procedure of Example 8 by substituting
the appropriate starting materials, reagents and reaction
conditions and include compounds selected from (wherein MS
represents mass spec as MH.sup.+, unless otherwise indicated, m.p.
represents melting point in .degree. C., and N/A indicates that the
data was not obtained):
TABLE-US-00012 Cpd Name m.p. MS 541
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)- 160-164 504.8
1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 601
6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H- 201-203 491.2
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 634
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2-yl)- N/A 505.1
1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 682
6-[3-cyano-6-(difluoromethoxy)-5-fluoro-1- N/A 556.9
(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide 704
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)- 195-198 519.1
1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide
Example 9
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclopentyl-5-fluoro-6-methyl-1H-
-indole-3-carboxamide (Cpd 683)
##STR00249##
Step A: A mixture of
3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-ylboronic acid
(125 mg, 0.42 mmol, 90%)[prepared as in Example 6, Step E],
N-tert-butyl-6-chloropyridine-3-sulfonamide (69 mg, 0.28 mmol),
tri-tert-butylphosphonium tetrafluoroborate (10 mg, 0.034 mmol),
Pd.sub.2(dba).sub.3 (16 mg, 0.017 mmol) and potassium fluoride (150
mg, 2.58 mmol) in THF (2.0 mL) was stirred at 40.degree. C.
overnight. The solvent was then evaporated and the residue purified
on silica gel eluting with 0 to 10% ethyl acetate in
CH.sub.2Cl.sub.2 to provide
N-tert-butyl-6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)pyr-
idine-3-sulfonamide (99 mg, 78%).
##STR00250##
Step B: Into a solution of
N-tert-butyl-6-(3-cyano-1-cyclopentyl-5-fluoro-6-methyl-1H-indol-2-yl)pyr-
idine-3-sulfonamide (90 mg, 0.2 mmol) in TFA (2.0 mL) was added 2
drops of water. The mixture was stirred at 40.degree. C. for 30 min
and then evaporated. The residue was purified on silica gel eluting
with 5 to 30% ethyl acetate in CH.sub.2Cl.sub.2 to provide the
title compound (19 mg, 20%). MS m/z 473.3 M+H.sup.+; .sup.1H NMR
(500 MHz, DMSO-d.sub.6): .delta. 9.10 (1H, dd, J=2.0, 1.0 Hz), 8.29
(1H, dd, J=10.5, 2.5 Hz), 7.89 (1H, s), 7.81 (1H, dd, J=8.5, 1.0
Hz), 7.59 (1H, d, J=10.5 Hz), 7.49 (1H, d, J=6.5 Hz), 7.02 (2H, br
s), 4.63-4.56 (1H, m), 2.46 (3H, s), 2.16-2.08 (2H, m), 1.96-1.85
(4H, m), 1.60-1.56 (2H, m), 1.17 (9H, s).
Additional compounds representative of the present invention may be
prepared according to the procedure of Example 9 by substituting
the appropriate starting materials, reagents and reaction
conditions and include compounds selected from (wherein MS
represents mass spec as MH.sup.+, unless otherwise indicated, m.p.
represents melting point in .degree. C., and N/A indicates that the
data was not obtained):
TABLE-US-00013 Cpd Name m.p. MS 552
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2- 204-205
419.2 yl]pyridine-3-sulfonamide 568
1-cyclobutyl-6-(difluoromethoxy)-2-(5-sulfamoylpyridin- 230-231
437.2 2-yl)-1H-indole-3-carboxamide 581
1-cyclobutyl-6-(difluoromethoxy)-2-{5-[(1,3- 211-213 515.3
difluoropropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-
carboxamide 582
1-cyclobutyl-6-cyclopropyl-2-{5-[(1,3-difluoropropan-2- N/A 489.3
yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-carboxamide 699
1-cyclopentyl-5-fluoro-6-methyl-2-(5-{[(2R)-1,1,1- 243-245 513.3
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 700 1-cyclopentyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-
244-246 512.8
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 701
1-cyclopentyl-5-fluoro-6-methyl-2-{5-[(1,1,1-trifluoro-2- 211-214
527.- 3 methylpropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-
carboxamide 703
1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-2-(5-{[(2S)- 184-186
550.8 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 706
1-cyclohexyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1- 273-279 527.3
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 707 1-cyclohexyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-
N/A 528.3 trifluoropropan-2-yl]sulfamoyl}pyrimidin-2-yl)-1H-indole-
3-carboxamide 714
1-cyclohexyl-5-fluoro-6-methyl-2-{5-[(1,1,1-trifluoro-2- 245-250
542.1- methylpropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-
carboxamide 715
1-cyclohexyl-5-fluoro-6-methyl-2-(5-sulfamoylpyridin-2- 254-257
432.0 yl)-1H-indole-3-carboxamide 716
1-cyclohexyl-5-fluoro-6-methyl-2-(5-{[(2R)-1,1,1- 272-276 528.0
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 718
1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-2-(5-{[(2R)- 218-220
565.4 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 723
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclobutyl-6- 158-160
511.3 (difluoromethoxy)-5-fluoro-1H-indole-3-carboxamide 729
1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-2-{5-[(1,1,1- 207-209
565.1 trifluoro-2-methylpropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-
indole-3-carboxamide 730 1-cyclopentyl-5-fluoro-6-methyl-2-(5-{[1-
220-221 525.3
(trifluoromethyl)cyclopropyl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 731
1-cyclobutyl-6-cyclopropyl-5-fluoro-2-(5-{[(2S)-1,1,1- 225-227
525.2 trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 732 1-cyclobutyl-5-fluoro-6-methyl-2-(5-{[(2R)-1,1,1-
195-197 499.2
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 733 5-chloro-1-cyclobutyl-6-methyl-2-(5-{[(2S)-1,1,1-
171-173 516.2
trifluoropropan-2-yl]sulfamoyl}pyrimidin-2-yl)-1H-indole-
3-carboxamide 734 5-chloro-1-cyclobutyl-6-methyl-2-(5-{[(2S)-1,1,1-
207-209 516.2
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 735 5-chloro-1-cyclobutyl-6-methyl-2-(5-{[(2R)-1,1,1-
208-210 515.2
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 736 6-chloro-1-cyclobutyl-5-fluoro-2-(5-{[(2S)-1,1,1-
241-243 519.2
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 737 1-cyclobutyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1-
190-194 499.2
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 745 5-chloro-1-cyclobutyl-2-[5-(propan-2- 245-247 448.2
ylsulfamoyl)pyrimidin-2-yl]-1H-indole-3-carboxamide 746
1-cyclohexyl-6-(difluoromethoxy)-2-(5-{[(2S)-1,1,1- 217-219 562.3
trifluoropropan-2-yl]sulfamoyl}pyrimidin-2-yl)-1H-indole-
3-carboxamide 747 1-cyclohexyl-6-(difluoromethoxy)-2-[5-(propan-2-
216-218 508.3 ylsulfamoyl)pyrimidin-2-yl]-1H-indole-3-carboxamide
748 5-fluoro-1-(pyridin-2-yl)-2-(5-{[(2S)-1,1,1- N/A 507.8
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 767
5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-2-(5- 258-262 529.2
{[(2R)-1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-
1H-indole-3-carboxamide 768
5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-2-{5- 200-206 543.2
[(1,1,1-trifluoro-2-methylpropan-2-yl)sulfamoyl]pyridin-
2-yl}-1H-indole-3-carboxamide 769
5-fluoro-6-methyl-1-(tetrahydro-2H-pyran-4-yl)-2-(5- 261-264 529.3
{[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-
1H-indole-3-carboxamide 798
1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-2-[5- 204-206 531.2
(phenylsulfamoyl)pyridin-2-yl]-1H-indole-3-carboxamide 806
1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-2-(5-{[(2S)- 220-222
565.1 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 809
1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-2-(5-{[1- 197-200 563.1
(trifluoromethyl)cyclopropyl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 825
1-cyclobutyl-6-(difluoromethoxy)-4-fluoro-2-(5-{[(2S)- 254-256
549.1 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 828
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclobutyl-5- 292-293
455.1 hydroxy-6-methyl-1H-indole-3-carboxamide 829
1-cyclopentyl-6-cyclopropyl-5-fluoro-2-(5-{[(2R)-1,1,1- 233-234
537.1 trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 830 1-cyclopentyl-6-ethyl-5-fluoro-2-(5-{[(2S)-1,1,1-
237-238 525.1
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 833 1-cyclobutyl-5-hydroxy-6-methyl-2-(5-{[(2S)-1,1,1-
256-258 495.1
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 834 1-cyclopentyl-5-methoxy-6-methyl-2-(5-{[(2R)-1,1,1-
273-275 523.1
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 838
1-cyclopentyl-6-cyclopropyl-5-fluoro-2-(5-{[(2S)-1,1,1- 255-257
537.5 trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 839
6-(difluoromethoxy)-4-fluoro-1-(propan-2-yl)-2-(5-{[(2S)- 197-198
537.- 1 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 840
1-(cyclopropylmethyl)-6-(difluoromethoxy)-4-fluoro-2-(5- 211-212
549.1- {[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-
1H-indole-3-carboxamide 841
1-cyclopentyl-5-hydroxy-6-methyl-2-(5-{[(2S)-1,1,1- 272-274 509.1
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 849
6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-2-(5-{[(2S)-1,1,1- 235-236
537.3 trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 850 1-cyclopentyl-6-cyclopropyl-5-fluoro-2-{5-[(1,1,1-
236-237 551.2
trifluoro-2-methylpropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-
indole-3-carboxamide 857 1-cyclohexyl-5-fluoro-6-methyl-2-(5-{[1-
273-274 539.1
(trifluoromethyl)cyclopropyl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 863
1-cyclopentyl-6-(difluoromethoxy)-5-fluoro-2-{5-[(1,1,1- 215-217
579.2- trifluoro-2-methylpropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-
indole-3-carboxamide 871
1-cyclopentyl-6-ethyl-5-fluoro-2-{5-[(1,1,1-trifluoro-2- 185-188
539.2- methylpropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-
carboxamide 872 1-cyclopentyl-6-ethyl-5-fluoro-2-(5-{[1- 196-197
537.2 (trifluoromethyl)cyclopropyl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 874
5-fluoro-6-methyl-1-(pyridin-2-yl)-2-(5-{[(2S)-1,1,1- 142-148 521.5
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 875
5-fluoro-6-methyl-1-(pyrazin-2-yl)-2-(5-{[(2S)-1,1,1- 162-169 522.5
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 876
5-fluoro-1-(5-fluoropyridin-2-yl)-6-methyl-2-(5-{[(2S)- 224-228
539.5 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 877
5-fluoro-1-(6-fluoropyridin-2-yl)-6-methyl-2-(5-{[(2S)- 210-214
539.5 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 902
5-fluoro-1-(3-fluoropyridin-2-yl)-6-methyl-2-(5-{[(2S)- 130-138
539.5 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 904
5-fluoro-6-methyl-1-(5-methylpyrazin-2-yl)-2-(5-{[(2S)- 202-208
536.5 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 905
5-fluoro-6-methyl-1-(4-methylpyrimidin-2-yl)-2-(5-{[(2S)- 205-210
536.- 5 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 906
5-fluoro-1-(4-methoxypyrimidin-2-yl)-6-methyl-2-(5- 167-174 552.5
{[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-
1H-indole-3-carboxamide 909
6-ethyl-5-fluoro-1-(pyridin-2-yl)-2-(5-{[(2S)-1,1,1- N/A 536.2
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 912
5-fluoro-6-methyl-1-(pyridazin-3-yl)-2-(5-{[(2S)-1,1,1- 176-181
522.5 trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 913
5-fluoro-6-methyl-1-(pyridin-3-yl)-2-(5-{[(2S)-1,1,1- 223-227 521.5
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 980
6-ethyl-5-fluoro-1-(4-methylpyridin-2-yl)-2-(5-{[(2S)- 137-145
550.3 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 981
6-ethyl-5-fluoro-1-(5-fluoropyridin-2-yl)-2-(5-{[(2S)- 200-204
554.3 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 982
6-ethyl-5-fluoro-1-(2-methylpyrimidin-4-yl)-2-(5-{[(2S)- 115-120
551.3- 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 994
6-ethyl-5-fluoro-1-(pyrazin-2-yl)-2-(5-{[(2S)-1,1,1- 120-127 537.3
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 995
6-ethyl-5-fluoro-1-(6-fluoropyridin-2-yl)-2-(5-{[(2S)- 230-233
554.3 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 996
5-chloro-1-cyclobutyl-2-(5-{[(2S)-1,1,1-trifluoropropan- 244-245
501.1- 2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide 997
1-cyclobutyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan-2- 224-227
485- .1 yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxamide 1019
6-ethyl-5-fluoro-1-(4-fluorophenyl)-2-(5-{[(2S)-1,1,1- 210-217
553.3 trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 1020
1-(4-chlorophenyl)-6-ethyl-5-fluoro-2-(5-{[(2S)-1,1,1- 240-247
569.2-- 571.2
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 1021
6-ethyl-5-fluoro-1-(4-methylphenyl)-2-(5-{[(2S)-1,1,1- 228-233
549.3 trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 1022
6-ethyl-5-fluoro-1-[4-(trifluoromethyl)phenyl]-2-(5-{[(2S)- 253-259
6- 03.3 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 1023
6-ethyl-5-fluoro-1-(3-fluorophenyl)-2-(5-{[(2S)-1,1,1- 233-238
554.0 trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 1024
6-ethyl-5-fluoro-1-(3-methylphenyl)-2-(5-{[(2S)-1,1,1- 179-189
550.1 trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 1025
6-ethyl-5-fluoro-1-(3-methoxyphenyl)-2-(5-{[(2S)-1,1,1- N/A 566.1
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 1026
6-ethyl-5-fluoro-1-[3-(trifluoromethyl)phenyl]-2-(5-{[(2S)- N/A
604.0- 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 1027
1-(3-chlorophenyl)-6-ethyl-5-fluoro-2-(5-{[(2S)-1,1,1- 200-205
569.2-- 571.2
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 1039
6-ethyl-5-fluoro-1-(5-methylpyridin-2-yl)-2-(5-{[(2S)- N/A 550.5
1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 1040
6-ethyl-5-fluoro-1-(pyridin-3-yl)-2-(5-{[(2S)-1,1,1- N/A 537.3
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 1041
6-ethyl-5-fluoro-1-(pyrimidin-4-yl)-2-(5-{[(2S)-1,1,1- N/A 537.2
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 1042
1-(3-chloropyridin-2-yl)-6-ethyl-5-fluoro-2-(5-{[(2S)- N/A 570.5
1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H- 572.5
indole-3-carboxamide
1043 1-(5-chloropyridin-2-yl)-6-ethyl-5-fluoro-2-(5-{[(2S)- 256-254
570.5 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H- 572.5
indole-3-carboxamide 1044
1-(5-chloropyridin-3-yl)-6-ethyl-5-fluoro-2-(5-{[(2S)- N/A 570.2
1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H- 572.2
indole-3-carboxamide 1045
6-ethyl-5-fluoro-1-(pyridin-4-yl)-2-(5-{[(2S)-1,1,1- 219-224 536.3
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 1046
6-ethyl-5-fluoro-1-(pyridazin-3-yl)-2-(5-{[(2S)-1,1,1- 206-212
537.3 trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 1047
6-ethyl-5-fluoro-1-(5-methylpyrimidin-2-yl)-2-(5-{[(2S)- 257-261
551.- 5 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 1048
1-(4-chloropyridin-2-yl)-6-ethyl-5-fluoro-2-(5-{[(2S)- 200-204
570.5 1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H- 572.5
indole-3-carboxamide
Example 10
6-(3-cyano-1-cyclopentyl-5-hydroxy-6-methyl-1H-indol-2-yl)-N-[(2R)-1,1,1-t-
rifluoropropan-2-yl]pyridine-3-sulfonamide (Cpd 693)
##STR00251##
Step A: To a solution of
(R)-6-(3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-pyridine-3-sulfonic
acid (2,2,2-trifluoro-1-methyl-ethyl)-amide (0.48 g, 1.05 mmol) in
acidic acid (3 mL) was added bromine (0.35 g, 2.1 mmol) dropwise.
The solution was stirred at 90.degree. C. for 30 min, cooled to
room temperature and then diluted with water (20 mL). The
precipitate was collected and washed thoroughly with water, then
dried to give
(R)-6-(5-bromo-3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-pyridine-3-s-
ulfonic acid (2,2,2-trifluoro-1-methyl-ethyl)-amide as a light
yellow solid (0.54 g, 93%).
##STR00252##
Step B: A mixture of
(R)-6-(5-bromo-3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-pyridine-3-s-
ulfonic acid (2,2,2-trifluoro-1-methyl-ethyl)-amide (0.54 g, 0.97
mmol), bis(pinacolato)diboron (0.5 g, 2.0 mmol),
PdCl.sub.2dppf-CH.sub.2Cl.sub.2 complex (16 mg, 0.02 mmol) and
potassium acetate (0.40 g, 4.0 mmol) in dioxane (5 mL) was stirred
at 80.degree. C. overnight. The mixture was then cooled to room
temperature, diluted with ethyl acetate and filtered through a
silica-celite pad. The filtrate was concentrated, dissolved in
acetone (10 mL) and cooled to 0.degree. C. Into this solution was
added an aqueous solution of Oxone (10 mL, 1.0 M). The mixture was
stirred at room temperature for 15 min and diluted with ethyl
acetate and water. The aqueous layer was extracted with ethyl
acetate. The organic extractions were combined and washed with aq.
NaHSO.sub.3 and brine, dried over Na.sub.2SO.sub.4, and
concentrated. Purification on silica gel eluting with 40% ethyl
acetate in hexane gave
(R)-6-(3-cyano-1-cyclopentyl-5-hydroxy-6-methyl-1H-indol-2-yl)-pyridine-3-
-sulfonic acid (2,2,2-trifluoro-1-methyl-ethyl)-amide as a yellow
solid (0.40 g, 84%); Melting point: 239-240.degree. C.; MS m/z
493.2 M+H.sup.+; .sup.1H NMR (500 MHz, CD.sub.3COCD.sub.3) .delta.
9.24 (dd, J=2.30, 0.65 Hz, 1H), 8.50 (dd, J=8.25, 2.35 Hz, 1H),
8.42 (s, 1H), 8.10 (dd, J=8.25, 0.85 Hz, 1H), 7.47 (bs, 1H), 7.54
(s, 1H), 7.15 (s, 1H), 5.30-5.26 (m, 1H), 4.40-4.35 (m, 1H), 2.40
(s, 3H), 2.34-2.31 (m, 2H), 2.16-2.14 (m, 2H), 2.10-2.07 (m, 2H),
1.74-1.72 (m, 2H), 1.21 (d, J=2.25 Hz, 3H).
Additional compounds representative of the present invention may be
prepared according to the procedure of Example 10 by substituting
the appropriate starting materials, reagents and reaction
conditions and include compounds selected from (wherein MS
represents mass spec as MH.sup.+, unless otherwise indicated, m.p.
represents melting point in .degree. C., and N/A indicates that the
data was not obtained):
TABLE-US-00014 Cpd Name m.p. MS 636
6-[5-chloro-3-cyano-1-cyclobutyl-6-(difluoromethoxy)- N/A 549.0
1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 646
6-[1-cyclobutyl-6-(difluoromethoxy)-5-methyl-1H-indol- 151-153
503.9 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 647
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-ethyl-1H- 160-162
543.0 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 658
6-[5-chloro-3-cyano-1-cyclobutyl-6-(difluoromethoxy)- 218-226 507.1
1H-indol-2-yl]-N-(1-methylcyclopropyl)pyridine-3- sulfonamide 659
2-[5-chloro-3-cyano-1-cyclobutyl-6-(difluoromethoxy)- 228-232 532.1
1H-indol-2-yl]-N-(1,3-difluoropropan-2-yl)pyrimidine-5- sulfonamide
660 6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-methyl- 168-170
529.2 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 669
6-(3-cyano-1-cyclopentyl-5-methoxy-6-methyl-1H-indol- 211-211.5
506.9 2-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 674
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-hydroxy- 174-177
530.9 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 675
6-(5-bromo-3-cyano-1-cyclopentyl-6-methyl-1H-indol-2- 204-204.5
555.2 yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 684
6-(5-bromo-3-cyano-1-cyclobutyl-6-hydroxy-1H-indol-2- 223-224 545.1
yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide 685
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5- N/A 561.2
(methylsulfanyl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide 692
6-(5-bromo-3-cyano-1-cyclopentyl-6-methyl-1H-indol-2- 226.5-227
555.2 yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide, 694
6-(3-cyano-1-cyclopentyl-5-methoxy-6-methyl-1H-indol- 210.5-211
507.3 2-yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 728
6-(1-cyclobutyl-5-fluoro-6-hydroxy-1H-indol-2-yl)-N- 193-195 458.2
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 757
6-(3-cyano-1-cyclobutyl-5-methoxy-6-methyl-1H-indol- 222-223 491.2
2-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide
796 6-(3-cyano-1-cyclobutyl-5-hydroxy-6-methyl-1H-indol-2- 193-195
477.0 yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
805 N-tert-butyl-6-(3-cyano-1-cyclobutyl-5-hydroxy-6- 211-213 437.1
methyl-1H-indol-2-yl)pyridine-3-sulfonamide 807
6-(3-cyano-1-cyclobutyl-5-hydroxy-6-methyl-1H-indol-2- 209-210
477.0 yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide
Example 11
N-tert-butyl-6-(6-ethyl-5-fluoro-3-(methylsulfonyl)-1-(pyrimidin-2-yl)-1H--
indol-2-yl)pyridine-3-sulfonamide (Cmp 869)
##STR00253##
Step A: A mixture of
N-tert-butyl-6-(6-ethyl-5-fluoro-3-1H-indol-2-yl)pyridine-3-sulfonamide
(300 mg, 0.80 mmol), 2-(methylthio)isoindoline-1,3-dione (198 mg,
1.04 mmol), MgBr.sub.2 (60 mg, 0.32 mmol), and DMA (1.5 mL) was
heated at 90.degree. C. for 15 hours. The reaction mixture was
diluted in water and was extracted into ethyl acetate. The organic
layer was washed with water and brine. The organic layer was dried
over MgSO.sub.4, filtered, and concentrated under reduced pressure.
Purification by silica gel chromatography (4:1 hexanes:ethyl
acetate) yielded
N-tert-butyl-6-(6-ethyl-5-fluoro-3-(methylthio)-1H-indol-2-yl)pyridine-3--
sulfonamide (328 mg, 97%) as a yellow solid.
##STR00254##
Step B: A suspension of
N-tert-butyl-6-(6-ethyl-5-fluoro-3-(methylthio)-1H-indol-2-yl)pyridine-3--
sulfonamide (250 mg, 0.60 mmol) in CHCl.sub.3 (4 mL) was cooled to
0.degree. C. m-CPBA (425 mg, 2.46 mmol) was added in one portion
and stirred at room temperature for 1 hour. The reaction mixture
was diluted in CH.sub.2Cl.sub.2, and washed with aq. NaHCO.sub.3.
The organic layer was dried over MgSO.sub.4, filtered, and
concentrated under reduced pressure. Purification by silica gel
chromatography (30-40% ethyl acetate in hexanes), followed by ether
trituration, yielded
N-tert-butyl-6-(6-ethyl-5-fluoro-3-(methylsulfonyl)-1H-indol-2-yl)pyridin-
e-3-sulfonamide (124 mg, 45%) as a white solid.
##STR00255##
Step C: A mixture of
N-tert-butyl-6-(6-ethyl-5-fluoro-3-(methylsulfonyl)-1H-indol-2-yl)pyridin-
e-3-sulfonamide (115 mg, 0.25 mmol), 2-bromopyrimidine (88 mg, 0.55
mmol), CuI (28 mg, 0.15 mmol), K.sub.2CO.sub.3 (160 mg, 1.15 mmol),
and DMF (0.5 mL) was heated at 110.degree. C. for 15 hours. The
reaction mixture was diluted in water and extracted into ethyl
acetate. The organic layer was washed with water and then with
brine. The organic layer was dried over MgSO.sub.4, filtered, and
concentrated under reduced pressure. Purification by silica gel
chromatography (40% ethyl acetate in hexanes) yielded
N-tert-butyl-6-(6-ethyl-5-fluoro-3-(methylsulfonyl)-1-(pyrimidin--
2-yl)-1H-indol-2-yl)pyridine-3-sulfonamide (121 mg, 91%) as a white
solid. Melting point: 244-248.degree. C.; MS m/z 532.2 M+H.sup.+;
.sup.1H NMR (DMSO-d.sup.6, 500 MHz): .delta. 8.82 (d, 1H, J=2 Hz),
8.73 (d, 2H, 5.0 Hz), 8.23 (dd, 1H, J=8.0 Hz, 2 Hz), 8.05 (d, 1H,
J=6.5 Hz), 7.96 (d, 1H, J=8 Hz), 7.87 (s, 1H), 7.76 (d, 1H, 10.5
Hz), 7.51 (t, 1H, J=5 Hz), 3.38 (s, 3H), 2.78 (q, 2H, J=7.5 Hz),
1.23 (t, 3H, 3.75 Hz), 1.13 (s, 9H).
Example 12
(S)-methyl
1-cyclopentyl-5-fluoro-6-methyl-2-(5-(N-(1,1,1-trifluoropropan--
2-yl)sulfamoyl)pyridin-2-yl)-1H-indole-3-carboxylate (Cmp 756)
##STR00256##
Step A: Into a solution of 6-bromo-5-fluoro-1H-indole (14.9 g, 70
mmol) in THF (160 mL) at 0.degree. C. was added
trichloroacetylchloride (7.4 mL, 90 mmol) dropwise. The mixture was
stirred at room temperature over the weekend, and then partitioned
between ethyl acetate and water. The ethyl acetate was washed with
HCl (1 N), dried and evaporated. The residue was dissolved in
methanol (500 mL), into which was added 50% KOH (5 mL) and the
mixture was refluxed for 6 hr. The mixture was then evaporated
until crystals started to come out and then filtered. The solid was
washed with methanol and collected to give the title compound (10.6
g). The filtrate was concentrated and triturated with
CH.sub.2Cl.sub.2 and hexane to give the second crop (3.8 g). The
mother liquor was purified by flash chromatography with
CH.sub.2Cl.sub.2 and ethyl acetate (0 to 20%) to give methyl
6-bromo-5-fluoro-1H-indole-3-carboxylate (0.75 g). The total yield
was about 80%.
##STR00257##
Step B: A mixture of methyl
6-bromo-5-fluoro-1H-indole-3-carboxylate (9.0 g, 33 mmol),
bromocyclopentane (5.3 mL, 49.6 mmol) and Cs.sub.2CO.sub.3 (21.5 g,
66 mmol) in DMF (40 mL) was stirred at 80.degree. C. overnight. The
mixture was then poured into ice water, filtered and washed with
water. The solid was collected and dried to give methyl
6-bromo-1-cyclopentyl-5-fluoro-1H-indole-3-carboxylate (10.3 g,
yield 91%), which was used in the next step without further
purification.
##STR00258##
Step C: A mixture of methyl
6-bromo-1-cyclopentyl-5-fluoro-1H-indole-3-carboxylate (3.4 g, 10
mmol), dimethylzinc (1.2 M, 16.7 mL, 20 mmol) and PdCl.sub.2dppf
(163 mg, 0.2 mmol) in dioxane (20 mL) was stirred at 88.degree. C.
for 2 hr under nitrogen atmosphere. The mixture was then cooled and
methanol was added in slowly followed by 2 N HCl. The mixture was
treated with ethyl acetate, washed with water and brine, dried and
evaporated. The residue was purified by flash chromatography with
dichloromethane and hexane (1:1) to give methyl
1-cyclopentyl-5-fluoro-6-methyl-1H-indole-3-carboxylate (2.66 g,
yield 97%).
##STR00259##
Step D: Into a solution of methyl
1-cyclopentyl-5-fluoro-6-methyl-1H-indole-3-carboxylate (2.64 g,
9.6 mmol) and triisopropylborate (4.0 mL, 17.28 mmol) in THF (40
mL) at -78.degree. C. was added LDA (1.5 M, 8.3 mL, 12.48 mmol)
dropwise. The mixture was stirred for 45 min, and then treated with
ice water and extracted with dichloromethane. The organic layer was
dried over sodium sulfate and evaporated to give
1-cyclopentyl-5-fluoro-3-(methoxycarbonyl)-6-methyl-1H-indol-2-ylboronic
acid as a semi-solid (3.1 g, .about.50% pure), which was used in
next step without further purification.
##STR00260##
Step E: A mixture of
1-cyclopentyl-5-fluoro-3-(methoxycarbonyl)-6-methyl-1H-indol-2-ylboronic
acid (2.2 mmol),
(S)-6-chloro-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide
(0.53 g, 1.83 mmol), PdCl.sub.2dppf (0.15 g, 0.183 mmol), aq.
K.sub.2CO.sub.3 (2.0 M, 3.6 mL, 7.2 mmol) in acetonitrile (10 mL)
was stirred at room temperature over the weekend. The mixture was
treated with ethyl acetate and washed with water and brine and then
concentrated. The residue was purified by flash chromatography with
0-15% ethyl acetate in CH.sub.2Cl.sub.2 to provide (S)-methyl
1-cyclopentyl-5-fluoro-6-methyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)sulfa-
moyl)pyridin-2-yl)-1H-indole-3-carboxylate (0.52 g, 54%). MS m/z
528.2 M+H.sup.+; .sup.1H NMR (500 MHz, CDCl.sub.3): .delta. 9.21
(1H, d, J=1.8 Hz), 8.25 (1H, dd, J=8.2 Hz, J=2.2 Hz), 7.87 (1H, d,
J=10.6 Hz), 7.73 (1H, d, J=8.2 Hz), 7.27 (1H, d, J=5.2 Hz), 5.09
(1H, d, J=9.6 Hz), 4.39-4.31 (1H, m), 4.17-4.10 (1H, m), 3.70 (3H,
s), 2.44 (3H, d, J=1.8 Hz), 2.41-2.36 (2H, m), 2.20-1.96 (4H, m),
1.67-1.63 (2H, m), 1.45 (3H, d, J=7.0 Hz).
Additional compounds representative of the present invention may be
prepared according to the procedure of Example 12 by substituting
the appropriate starting materials, reagents and reaction
conditions and include compounds selected from (wherein MS
represents mass spec as MH.sup.+ (unless otherwise indicated), m.p.
represents melting point in .degree. C. and N/A indicates that the
data was not obtained):
TABLE-US-00015 Cpd Name m.p. MS 717 methyl
1-cyclohexyl-5-fluoro-2-(5-{[(2S)-1,1,1- 232-240 528.2
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-
1H-indole-3-carboxylate 754 methyl
1-cyclopentyl-5-fluoro-6-methyl-2-{5- N/A 542.2
[(1,1,1-trifluoro-2-methylpropan-2-
yl)sulfamoyl]pyridin-2-yl}-1H-indole-3- carboxylate 755 methyl
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1- N/A 488.3
cyclopentyl-5-fluoro-6-methyl-1H-indole-3- carboxylate 770 methyl
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1- N/A 474.3
cyclobutyl-5-fluoro-6-methyl-1H-indole-3- carboxylate 771 methyl
1-cyclobutyl-5-fluoro-6-methyl-2-(5- N/A 514.2
{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyridin-2-yl)-1H-indole-3- carboxylate 774 methyl
1-cyclobutyl-5-fluoro-6-methyl-2-(5- N/A 515.2
{[(2S)-1,1,1-trifluoropropan-2-
yl]sulfamoyl}pyrimidin-2-yl)-1H-indole-3- carboxylate 1099 methyl
2-{6-[(tert-butylsulfonyl)amino]pyridin- 166-167 356.0
3-yl}-1-cyclohexyl-5-fluoro-6-(fluoromethoxy)-
1H-indole-3-carboxylate
Example 13
(S)-1-cyclopentyl-5-fluoro-6-methyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)su-
lfamoyl)pyridin-2-yl)-1H-indole-3-carboxylic acid (Cmp 758)
##STR00261##
A mixture of (S)-methyl
1-cyclopentyl-5-fluoro-6-methyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)sulfa-
moyl)pyridin-2-yl)-1H-indole-3-carboxylate (0.45 g, 0.85 mmol), 25%
aq. NaOH (2.0 mL) in ethanol (4.0 mL) was stirred at 80.degree. C.
overnight. The mixture was then treated with water and extracted
with ether. The aqueous layer was acidified with 1N HCl to pH 4 and
extracted with ethyl acetate. The organic layers were washed with
brine, dried over Na.sub.2SO.sub.4 and evaporated to
give(S)-1-cyclopentyl-5-fluoro-6-methyl-2-(5-(N-(1,1,1-trifluoropropan-2--
yl)sulfamoyl)pyridin-2-yl)-1H-indole-3-carboxylic acid (0.36 g,
82%). MS m/z 514.2 M+H.sup.+; .sup.1H NMR (500 MHz,
acetone-d.sub.6): .delta. 10.55 (1H, br s), 9.17 (1H, d, J=2.2 Hz),
8.38 (1H, dd, J=8.2 Hz, J=2.2 Hz), 7.96 (1H, dd, J=8.2, 0.8 Hz),
7.89 (1H, d, J=10.7 Hz), 7.70 (br s, 1H), 7.57 (1H, d, J=6.4 Hz),
4.63-4.56 (1H, m), 4.34-4.29 (1H, m), 2.44 (3H, d, J=1.8 Hz),
2.29-2.25 (2H, m), 2.10-1.90 (4H, m), 1.67-1.56 (2H, m), 1.25 (3H,
d, J=7.0 Hz).
Additional compounds representative of the present invention may be
prepared according to the procedure of Example 13 by substituting
the appropriate starting materials, reagents and reaction
conditions and include compounds selected from (wherein MS
represents mass spec as MH.sup.+ (unless otherwise indicated), m.p.
represents melting point in .degree. C. and N/A indicates that the
data was not obtained):
TABLE-US-00016 Cpd Name m.p. MS 741
1-cyclohexyl-5-fluoro-2-(5-{[(2S)-1,1,1-trifluoropropan- 216-220
514.2- 2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-carboxylic acid 765
1-cyclopentyl-5-fluoro-6-methyl-2-{5-[(1,1,1-trifluoro-2- 233-234
528.- 2 methylpropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-3-
carboxylic acid 766
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclopentyl-5- 238-240
474.2- fluoro-6-methyl-1H-indole-3-carboxylic acid 775
1-cyclobutyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1- N/A 500.7
trifluoropropan-2-yl]sulfamoyl}pyrimidin-2-yl)-1H-indole-
3-carboxylic acid 776
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclobutyl-5- N/A 459.7
fluoro-6-methyl-1H-indole-3-carboxylic acid 793
1-cyclobutyl-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1- 234-240 500.6
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxylic acid 794
2-[5-(tert-butylsulfamoyl)pyrimidin-2-yl]-1-cyclobutyl-5- 194-201
461.- 2 fluoro-6-methyl-1H-indole-3-carboxylic acid 835
1-cyclohexyl-5-fluoro-6-methyl-2-(5-{[1- 205-213 540.7
(trifluoromethyl)cyclopropyl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxylic acid 928
1-cyclohexyl-6-(difluoromethoxy)-5-fluoro-2-{5-[(1,1,1- N/A 594.3
trifluoro-2-methylpropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-
indole-3-carboxylic acid 998
2-{5-[(tert-butylsulfonyl)amino]pyridin-2-yl}-1- 224-226 502.3
cyclohexyl-6-ethyl-5-fluoro-1H-indole-3-carboxylic acid 1028
2-{5-[(tert-butylsulfonyl)amino]pyrimidin-2-yl}-1- 236-237 503.6
cyclohexyl-6-ethyl-5-fluoro-1H-indole-3-carboxylic acid 1029
2-{2-[(tert-butylsulfonyl)amino]pyrimidin-5-yl}-1- N/A 503.6
cyclohexyl-6-ethyl-5-fluoro-1H-indole-3-carboxylic acid 1036
2-{2-[(tert-butylsulfonyl)amino]pyrimidin-5-yl}-1- >300 502.6
cyclohexyl-6-ethyl-5-fluoro-1H-indole-3-carboxamide 1037
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1- 297-299 501.7
cyclohexyl-6-ethyl-5-fluoro-1H-indole-3-carboxamide 1064
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1- N/A 540.6
cyclohexyl-6-(difluoromethoxy)-5-fluoro-1H-indole-3- carboxylic
acid 1080 2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-[(1S)-1-
N/A 526.3 cyclopropylethyl]-6-(difluoromethoxy)-5-fluoro-1H-
indole-3-carboxylic acid 1084
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-[(1R)-1- N/A 526.1
cyclopropylethyl]-6-(difluoromethoxy)-5-fluoro-1H-
indole-3-carboxylic acid 1086
2-{6-[(tert-butylsulfonyl)amino]-4-methylpyridin-3-yl}-1- N/A 540.7
[(1R)-1-cyclopropylethyl]-6-(difluoromethoxy)-5-fluoro-
1H-indole-3-carboxylic acid 1093
2-{6-[(tert-butylsulfonyl)amino]-2-methylpyridin-3-yl}-6- N/A 514.8
(difluoromethoxy)-5-fluoro-1-(propan-2-yl)-1H-indole-3- carboxylic
acid 1094 2-{6-[(tert-butylsulfonyl)amino]-2-methylpyridin-3-yl}-1-
N/A 540.2 [(1R)-1-cyclopropylethyl]-6-(difluoromethoxy)-5-fluoro-
1H-indole-3-carboxylic acid 1103
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-[(1R)-1-
165-decomp. - 488.5 cyclopropylethyl]-6-ethyl-5-fluoro-1H-indole-3-
carboxylic acid
Example 14
(S)-1-cyclopentyl-5-fluoro-N,6-dimethyl-2-(5-(N-(1,1,1-trifluoropropan-2-y-
l)sulfamoyl)pyridin-2-yl)-1H-indole-3-carboxamide (Cmp 761)
##STR00262##
A mixture of
(S)-1-cyclopentyl-5-fluoro-6-methyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)s-
ulfamoyl)pyridin-2-yl)-1H-indole-3-carboxylic acid (300 mg, 0.58
mmol) in SOCl.sub.2 (4 mL) was stirred at 66.degree. C. for 2 h.
Volatiles were removed by a stream of nitrogen followed by vacuum
to give
(S)-1-cyclopentyl-5-fluoro-6-methyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)s-
ulfamoyl)pyridin-2-yl)-1H-indole-3-carbonyl chloride as a solid.
The above prepared
(S)-1-cyclopentyl-5-fluoro-6-methyl-2-(5-(N-(1,1,1-trifluoroprop-
an-2-yl)sulfamoyl)pyridin-2-yl)-1H-indole-3-carbonyl chloride (100
mg, 0.188 mmol) was treated with a solution of methylamine in THF
(2.0 M, 5 mL, 10 mmol) and stirred at room temperature for 5 min.
The mixture was then treated with ethyl acetate, washed with water
and brine, dried over Na.sub.2SO.sub.4 and evaporated to give
(S)-1-cyclopentyl-5-fluoro-N,6-dimethyl-2-(5-(N-(1,1,1-trifluoropropan-2--
yl)sulfamoyl)pyridin-2-yl)-1H-indole-3-carboxamide (66 mg, 67%). MS
m/z 527.3 M+H.sup.+; .sup.1H NMR (500 MHz, CDCl.sub.3): .delta.
9.18 (1H, br s), 8.30 (1H, dd, J=8.0 Hz, J=2.0 Hz), 7.73 (1H, d,
J=8.5 Hz), 7.66 (1H, d, J=10.5 Hz), 7.28 (1H, br s), 6.26 (1H, br
s), 5.91 (1H, d, J=9.5 Hz), 4.51-4.40 (1H, m), 4.15-4.10 (1H, m),
2.84 (3H, s), 2.43 (3H, d, J=1.5 Hz), 2.30-2.23 (2H, m), 2.10-1.90
(4H, m), 1.68-1.62 (2H, m), 1.42 (3H, d, J=8.5 Hz).
Additional compounds representative of the present invention may be
prepared according to the procedure of Example 14 by substituting
the appropriate starting materials, reagents and reaction
conditions and include compounds selected from (wherein MS
represents mass spec as MH.sup.+ (unless otherwise indicated), m.p.
represents melting point in .degree. C. and N/A indicates that the
data was not obtained):
TABLE-US-00017 Cpd Name m.p. MS 762
1-cyclopentyl-N-ethyl-5-fluoro-6-methyl-2-(5-{[(2S)- 160-162 541.3
1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 763
1-cyclopentyl-5-fluoro-6-methyl-N-(propan-2-yl)-2-(5- 234-236 555.3
{[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-
1H-indole-3-carboxamide 783
1-cyclopentyl-5-fluoro-N,N,6-trimethyl-2-(5-{[(2S)-1,1,1- 278-280
541.- 2 trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 795
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclobutyl-5- 215-218
473.2 fluoro-N,6-dimethyl-1H-indole-3-carboxamide 799
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclopentyl-5- 248-250
487.3- fluoro-N,6-dimethyl-1H-indole-3-carboxamide 800
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclobutyl-5- 189-193
459.3 fluoro-6-methyl-1H-indole-3-carboxamide 801
1-cyclobutyl-5-fluoro-N,6-dimethyl-2-(5-{[(2S)-1,1,1- N/A 513.2
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 802
2-[5-(tert-butylsulfamoyl)pyrimidin-2-yl]-1-cyclobutyl-5- 211-213
474.- 2 fluoro-N,6-dimethyl-1H-indole-3-carboxamide 999
2-{5-[(tert-butylsulfonyl)amino]pyridin-2-yl}-1- 264-265 501.4
cyclohexyl-6-ethyl-5-fluoro-1H-indole-3-carboxamide 1063
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1- 296-297 539.6
cyclohexyl-6-(difluoromethoxy)-5-fluoro-1H-indole-3- carboxamide
1081 2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-[(1S)-1-
239-241 525.- 4 cyclopropylethyl]-6-(difluoromethoxy)-5-fluoro-1H-
indole-3-carboxamide 1085
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-[(1R)-1- 228-230
525.- 1 cyclopropylethyl]-6-(difluoromethoxy)-5-fluoro-1H-
indole-3-carboxamide 1087
2-{6-[(tert-butylsulfonyl)amino]-4-methylpyridin-3-yl}-1- 250-254
539- .4 [(1R)-1-cyclopropylethyl]-6-(difluoromethoxy)-5-fluoro-
1H-indole-3-carboxamide 1095
2-{6-[(tert-butylsulfonyl)amino]-2-methylpyridin-3-yl}-6- 234-235
513- .4 (difluoromethoxy)-5-fluoro-1-(propan-2-yl)-1H-indole-3-
carboxamide 1096
2-{6-[(tert-butylsulfonyl)amino]-2-methylpyridin-3-yl}-1- 147-151
539- .2 [(1S)-1-cyclopropylethyl]-6-(difluoromethoxy)-5-fluoro-
1H-indole-3-carboxamide 1100
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-6- 272-274 507.3
cyclopropyl-5-fluoro-1-phenyl-1H-indole-3-carboxamide 1102
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1- 274-276 521.0
cyclohexyl-5-fluoro-6-(fluoromethoxy)-1H-indole-3- carboxamide 1104
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-[(1R)-1-
255.5-259.0 - 487.5 cyclopropylethyl]-6-ethyl-5-fluoro-1H-indole-3-
carboxamide
Example 15
N-tert-butyl-6-(3,6-diacetyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl)pyr-
idine-3-sulfonamide (Cmp 939)
##STR00263##
Step A: Into a suspension of
6-(6-bromo-5-fluoro-1H-indol-2-yl)-N-tert-butylpyridine-3-sulfonamide
(2.4 g, 5.6 mmol) in acetonitrile (5.6 mL) and DMF (11.2 mL) at
0.degree. C. was added chlorosulfonyl isocyanate (0.97 mL, 11.2
mmol) dropwise. The mixture was stirred at 0.degree. C. for 15 min
and then 30 min at room temperature. The reaction was quenched by
addition of ice water. The mixture was extracted with ethyl
acetate, dried and concentrated. The residue was treated with
dichloromethane and filtered. The solid was collected as a mixture
of
6-(6-bromo-3-cyano-5-fluoro-1H-indol-2-yl)-N-tert-butylpyridine-3-sulfona-
mide and
6-(6-bromo-3-chloro-5-fluoro-1H-indol-2-yl)-N-tert-butylpyridine--
3-sulfonamide, which was used in the next step without further
purification.
##STR00264##
Step B: The mixture prepared as above (0.71 g) was mixed with
2-bromopyrimidine (0.5 g, 3.14 mmol), potassium carbonate (0.65 g,
4.71 mmol) and CuI (60 mg, 0.314 mmol) in DMF (2.0 mL) was stirred
at 110.degree. C. for 24 hr under nitrogen atmosphere. The mixture
was then treated with ethyl acetate, washed with aqueous ammonium
chloride and brine, dried over sodium sulfate and evaporated. The
residue was purified with dichloromethane and ethyl acetate (0 to
8%) to give a mixture (0.6 g) of
6-(6-bromo-3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl)-N-ter-
t-butylpyridine-3-sulfonamide (.about.86%) and
6-(6-bromo-3-chloro-5-fluoro-1-1.0
(pyrimidin-2-yl)-1H-indol-2-yl)-N-tert-butylpyridine-3-sulfonamide
(.about.14%), which was used in the next step reaction without
further purification.
##STR00265##
Step C: A mixture of
6-(6-bromo-3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl)-N-tert-buty-
lpyridine-3-sulfonamide and
6-(6-bromo-3-chloro-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl)-N-tert-but-
ylpyridine-3-sulfonamide (84 mg, 0.156 mmol), Pd(OAc).sub.2 (7.6
mg, 0.034 mmol), 1,3-bis(diphenylphosphino)propane (31 mg, 0.075
mmol), K.sub.2CO.sub.3 (0.19 g, 1.36 mmol), butyl vinyl ether (0.73
mL, 5.66 mmol) in DMF (3.0 mL) and water (0.35 mL) was stirred at
120.degree. C. overnight under N.sub.2 atmosphere. The mixture was
then acidified to pH .about.1 with 1 N HCl, stirred at room
temperature for 1 hr, extracted with ethyl acetate followed by
drying with Na.sub.2SO.sub.4, evaporation and purification by flash
chromatography with 5 to 20% ethyl acetate in CH.sub.2Cl.sub.2 to
give
N-tert-butyl-6-(3,6-diacetyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl)py-
ridine-3-sulfonamide (58 mg, 73%). MS m/z 510.1 M+H.sup.+; .sup.1H
NMR (500 MHz, acetone-d.sub.6): .delta. 9.07 (1H, d, J=2.2 Hz),
8.77 (1H, d, J=6.2 Hz), 8.58 (2H, d, 4.9 Hz), 8.28 (1H, dd, J=8.2,
2.2 Hz), 8.12 (1H, d, J=10.2 Hz), 7.78 (1H, dd, J=8.2, 0.7 Hz),
7.21 (1H, t, J=4.9 Hz), 4.80 (1H, br s), 2.75 (3H, d, J=5.4 Hz),
2.21 (3H, s), 1.25 (9H, s).
Example 16
Cmp 883
##STR00266##
A pressure vessel was charged with
(S)-6-(3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl)-N-(1,1,1--
trifluoropropan-2-yl)pyridine-3-sulfonamide (600 mg, 1.25 mmol),
aq. NaOH (50%, 2 mL) and ethanol (2 mL). The mixture was sealed and
heated to 120.degree. C. over night. After cooling the reaction
mixture was poured into ice water (20 mL), and extracted with ethyl
acetate, dried over MgSO.sub.4 and purified by silica gel
chromatography to afford
2-(5-(N-tert-butylsulfamoyl)pyridin-2-yl)-6-ethyl-5-fluoro-1-(pyridin-2-y-
l)-1H-indole-3-carboxamide (315 mg, 51%). MS m/z 496.2 M+H.sup.+;
.sup.1H NMR (500 MHz, CDCl.sub.3): .delta. 8.84 (1H, m), 8.31 (1H,
m), 8.02 (1H, q, J=4.0 Hz), 7.79 (1H, m), 7.76 (1H, s), 7.50 (1H,
dd, J=3.75 Hz, 3.74 Hz), 7.31 (1H, d, J=3.6 Hz), 7.26 (2H, m), 7.21
(1H, m), 6.58 (1H, s), 2.63 (2H, q, J=1.3 Hz), 1.09 (9H, s), 1.02
(3H, t, J=2.4 Hz).
Additional compounds representative of the present invention may be
prepared according to the procedure of Example 16 by substituting
the appropriate starting materials, reagents and reaction
conditions and include compounds selected from (wherein MS
represents mass spec as MH.sup.+ (unless otherwise indicated), m.p.
represents melting point in .degree. C. and N/A indicates that the
data was not obtained):
TABLE-US-00018 Cpd Name m.p. MS 846
5-methyl-1-(pyrimidin-2-yl)-2-(5-{[(2S)-1,1,1- N/A 505.2
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 916 5-methyl-1-(pyrazin-2-yl)-2-(5-{[(2S)-1,1,1-
240-245 505.2
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 918
6-fluoro-5-methyl-1-(pyrimidin-2-yl)-2-(5-{[(2S)-1,1,1- 245-249
523.2 trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indole-3-
carboxamide 978
6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-2-{5-[(1,1,1-trifluoro- 261-269
55- 1.3 2-methylpropan-2-yl)sulfamoyl]pyridin-2-yl}-1H-indole-
3-carboxamide 979 6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-2-(5-{[1-
240-247 549.2
(trifluoromethyl)cyclopropyl]sulfamoyl}pyridin-2-yl)-1H-
indole-3-carboxamide 1083
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-[(1S)-1-
256.0-259.0 - 487.5 cyclopropylethyl]-6-ethyl-5-fluoro-1H-indole-3-
carboxamide 1088 2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-1-
290-294 513.7 cyclohexyl-6-cyclopropyl-4-fluoro-1H-indole-3-
carboxamide 1097 2-{5-[(tert-butylsulfonyl)amino]pyridin-2-yl}-1-
275-285 513.4 cyclohexyl-6-cyclopropyl-4-fluoro-1H-indole-3-
decomp. carboxamide range 1105
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-6- 290-295 525.3
cyclopropyl-4-fluoro-1-(4-fluorophenyl)-1H-indole-3- carboxamide
1106 2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-6-ethyl-4-
280-288 513.- 3 fluoro-1-(4-fluorophenyl)-1H-indole-3-carboxamide
1109 2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-6-ethyl-5-fluoro-1-
237.9-238- .9 493.3 phenyl-1H-indole-3-carboxamide 1110
2-{5-[(tert-butylsulfonyl)amino]pyridin-2-yl}-1-cyclobutyl- 259-263
4- 73.3 6-ethyl-4-fluoro-1H-indole-3-carboxamide 1111
2-{6-[(tert-butylsulfonyl)amino]pyridin-3-yl}-6-ethyl-4- 288-294
495.- 2 fluoro-1-phenyl-1H-indole-3-carboxamide 1115
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-1-cyclohexyl-5- 274.5-275.6
4- 87.4 fluoro-6-methyl-1H-indole-3-carboxamide 1116
2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-5-fluoro-6-methyl-
241.2-242.- 5 479.3 1-phenyl-1H-indole-3-carboxamide
Example 17
Cmp 810
##STR00267##
Step A: A mixture of
(S)-6-(3-cyano-1-cyclobutyl-5-fluoro-6-hydroxy-1H-indol-2-yl)-N-(1,1,1-tr-
ifluoropropan-2-yl)pyridine-3-sulfonamide (31.9 g, 66.2 mmol), 5 N
aq. NaOH (25 mL), and isopropanol (140 mL) was stirred at
60.degree. C. Chlorodifluoromethane gas was bubbled into this
mixture at a constant rate. Heating continued for 10 hours, with
additional 5 N aq. NaOH (3 mL) being added in 30 minute increments.
The reaction mixture was diluted in H.sub.2O (800 mL) and was
acidified with 6 N aq. HCl. This was extracted with EtOAc
(2.times.200 mL). The combined organic extracts were washed with
water (2.times.300 mL), then brine (50 mL). The organic layer was
subsequently dried over MgSO.sub.4 and filtered, and the filtrate
was concentrated under vacuum. The product mixture was redissolved
in CH.sub.2Cl.sub.2 (500 mL), and was absorbed onto silica (100 g).
CH.sub.2Cl.sub.2 was removed under vacuum. The solids were loaded
onto a column of 100 g additional silica. Elution with
CH.sub.2Cl.sub.2/hexanes (1:1 to 3:1), and then with ethyl acetate
in CH.sub.2Cl.sub.2 (0% to 5%) yielded 28.6 g crude product. This
was washed with Et.sub.2O (100 mL) to yield
(S)-6-(3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-
-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (25.6 g,
72%) as a white solid.
##STR00268##
Step B: A mixture of
(S)-6-(3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl)-N-
-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (500 mg, 0.94
mmol), Fe powder (700 mg, 13 mmol), Br.sub.2 (300 .mu.L, 5.9 mmol),
and 1,2-dichloroethane (3 mL) was heated at 50.degree. C. for 3
hours. The reaction mixture was then poured into aq. NaHSO.sub.3
solution. This was extracted into CH.sub.2Cl.sub.2. The organic
layer was dried over MgSO.sub.4 and filtered, and the filtrate was
concentrated under vacuum. Purification by silica gel
chromatography (ethyl acetate in hexanes, 20% to 30%) yielded
(S)-6-(4-bromo-3-cyano-1-cyclobutyl-6
(difluoromethoxy)-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)p-
yridine-3-sulfonamide (266 mg, 46%) as a white solid.
##STR00269##
Step C: A solution of MeZnCl (2 M in THF, 370 .mu.L, 0.74 mmol) was
added to a mixture of (S)-6-(4-bromo-3-cyano-1-cyclobutyl-6
(difluoromethoxy)-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)p-
yridine-3-sulfonamide (200 mg, 0.33 mmol), Pd(dppf)Cl.sub.2 (25 mg,
0.034 mmol), and THF (1.2 mL). This was heated at 40.degree. C. for
25 hours. The reaction mixture was then poured onto aq. HCl. This
was extracted with ethyl acetate and the organic layer was washed
with brine. The organic layer was dried over MgSO.sub.4 and
filtered, and the filtrate was concentrated under vacuum.
Purification by silica gel chromatography (20% ethyl acetate in
hexanes), followed by washing with hexanes/ether (1:1) yielded
(S)-6-(3-cyano-1-cyclobutyl-6
(difluoromethoxy)-5-fluoro-4-methyl-1H-indol-2-yl)-N-(1,1,1-trifluoroprop-
an-2-yl)pyridine-3-sulfonamide (117 mg, 65%) as a white solid.
Melting point: 182-186.degree. C.; MS m/z 547.0 M+H.sup.+; .sup.1H
NMR (CDCl.sub.3, 500 MHz): .delta. 9.22 (d, 1H, J=2 Hz), 8.35 (dd,
2H, J=8.5 Hz, 2 Hz), 8.02 (d, 1H, 8.5 Hz), 7.40 (d, 1H, J=6.5 Hz),
6.62 (t, 1H, J=75 Hz), 5.26 (pentet, 1H, J=8.5 Hz), 4.95 (d, 1H,
J=9.5 Hz), 4.16 (m, 1H), 2.75 (d, 3H, J=2.0 Hz), 2.47 (m, 2H), 2.38
(m, 2H), 1.87 (m, 2H), 1.47 (d, 3H, J=7 Hz). Cpd 811 was prepared
as in Example 17 except the bromination and freonation steps of
that sequence were reversed.
TABLE-US-00019 Cpd Name m.p. MS 811
6-[3-cyano-1-cyclobutyl-6-(difluoromethoxy)- 168-174 547.1
5-fluoro-7-methyl-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide
Example 18
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-yl)-N-[(2S)-1,1,1-tri-
fluoro(2-deuterium)propan-2-yl]pyridine-3-sulfonamide (Cmp
1113)
##STR00270##
Step A: To a solution of p-toluenesulfonic acid monohydrate (3 g,
16 mmol) and 2-methyltetrahydrofuran (600 mL) were added
(S,L)-alpha methylbenzylamine (40 g, 310 mmol),
tetraethylorthosilicate (28 mL, 125 mmol), and
1,1,1-trifluoroacetone (65 mL, 690 mmol). The mixture was stirred
at reflux for 17 hours and at 0.degree. C. for 1 hour. The mixture
was filtered through a thin pad of silica gel, and the filter cake
was rinsed with EtOAc. The filtrate was concentrated using a rotary
evaporator and used without further purification.
##STR00271##
Step B: The residue from above was added as a solution in THF (130
mL), dropwise over 1 hour, to a suspension of lithium aluminum
deuteride (34.9 g, 831 mmol) in THF (700 mL) at 0.degree. C. The
mixture was stirred at 0.degree. C. for 1 hour and at room
temperature for 2 hours. The mixture was then cooled back to
0.degree. C., MTBE (400 mL) was added, followed by the slow,
sequential addition of H.sub.2O (35 mL), aq. NaOH (5 N, 35 mL), and
H.sub.2O (105 mL). The mixture was stirred at room temperature for
15 minutes, MgSO.sub.4 was added, and the mixture was stirred at
room temperature for an additional 15 minutes. The mixture was
filtered through Celite and the filter cake was rinsed with EtOAc.
The filtrate was concentrated and the residue was transferred to a
separatory funnel. MTBE (500 mL) and aq. HCl (3 N, 500 mL) were
added and the organic layer was extracted with aq. HCl (3 N,
2.times.250 mL). The combined aqueous layers were cooled to
0.degree. C., aq. NaOH (50%, 200 mL) was added, the mixture was
transferred to a separatory funnel, and the aqueous layer was
extracted with CH.sub.2Cl.sub.2 (3.times.500 mL). The combined
organic layers were dried with Na.sub.2SO.sub.4 and concentrated
using a rotary evaporator. The residue was passed through a silica
gel plug, eluting with hexanes, to provide
(S)-1,1,1-trifluoro-2-deutero-N--((S)-1-phenylethyl)propan-2-amine
(34.2 g, 50% from (S,L-)-alpha-methylbenzylamine).
##STR00272##
Step C: To a mixture of
(S)-1,1,1-trifluoro-2-deutero-N-((S)-1-phenylethyl)propan-2-amine
(34.2 g, 157 mmol) dissolved in MeOH (475 mL) was added 10% Pd/C (5
g, 4.7 mmol). The mixture was hydrogenated at room temperature
under 1 atmosphere of hydrogen gas for 20 h. The mixture was
gravity filtered through Celite, rinsing the filter cake with
EtOAc. The filtrate was cooled to 0.degree. C., and HCl (4 M in
dioxane, 235 mL) was added. The solution was concentrated using a
rotary evaporator to provide
(S)-1,1,1-trifluoro-2-deutero-propan-2-amine hydrochloride (22.9 g,
97%). (S)-1,1,1-trifluoro-2-deutero-propan-2-amine hydrochloride
(25.0 g, 165.7 mmol) was added to H.sub.2O (100 mL), and the
mixture was cooled to 0.degree. C. To the mixture was added aq.
NaOH (50%, 45 mL), dropwise over 10 minutes, and material was
distilled out of this solution at ca. 50.degree. C., providing
(S)-1,1,1-trifluoro-2-deutero-propan-2-amine (15.7 g, 67%, 53.3%
ee, containing ca. 19 wt % H.sub.2O). This material was added to
D-tartaric acid (25 g, 170 mmol, 99.8% ee) and MeOH (300 mL), and
the mixture was stirred at reflux for 30 minutes. The mixture was
cooled slowly to 0.degree. C., allowing crystals to form. The
crystals were isolated by filtration, providing
(S)-1,1,1-trifluoro-2-deutero-propan-2-amine tartrate salt (28.4 g,
84%, 84.0% ee, containing ca. 4% MeOH and 9 wt % H.sub.2O). This
material was recrystallized from MeOH (230 mL), providing
(S)-1,1,1-trifluoro-2-deutero-propan-2-amine tartrate salt (24.3 g,
85%, 95.7% ee, ca. 9% MeOH and 5 wt % H.sub.2O). This material was
again recrystallized from MeOH (200 mL), providing
(S)-1,1,1-trifluoro-2-deutero-propan-2-amine tartrate salt (20.7 g,
85%, 98.7% ee, ca. 5% MeOH and 10 wt % H.sub.2O). This material was
added to H.sub.2O (150 mL), and the mixture was cooled to 0.degree.
C. NaOH (50%, 18 mL) was added, dropwise over 5 minutes, and 6.7 g
of material was distilled out of the solution at ca. 49.degree. C.
This material was cooled to 0.degree. C. and concentrated aq. HCl
(15 mL) was added. The mixture was stirred at room temperature for
25 minutes and then concentrated using a rotary evaporator
(azeotropic removal of H.sub.2O using MeOH and EtOH), providing
(S)-1,1,1-trifluoro-2-deutero-propan-2-amine hydrochloride (8.7 g,
87% from (S)-1,1,1-trifluoro-2-deutero-propan-2-amine tartrate
salt, 98.6% ee).
##STR00273##
Step D: (S)-1,1,1-trifluoro-2-deutero-propan-2-amine hydrochloride
(3 g, 19.9 mmol, 98.6% ee) was converted into
(S)-6-chloro-N-(1,1,1-trifluoro-2-deutero-propan-2-yl)pyridine-3-sulfonam-
ide (5.3 g, 91%) in a manner analogous to Example 1B.
##STR00274##
Step E: 1-cyclobutyl-5-fluoro-6-methyl-1H-indole-3-carbonitrile
(133 mg, 0.58 mmol) was converted into
3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-ylboronic acid in
a manner analogous to Example 7D and used without further
purification.
##STR00275##
Step F:
(S)-6-chloro-N-(1,1,1-trifluoro-2-deutero-propan-2-yl)pyridine-3--
sulfonamide (100 mg, 0.35 mmol) and
3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H-indol-2-ylboronic acid
were converted into Compound 1113 (34 mg, 20%) in a manner
analogous to Example 7E. Melting point: 215-217.degree. C.; MS m/z
482.0 M-1-H.sup.+; .sup.1H NMR (500 MHz, acetone-d.sub.6) .delta.
9.21 (1H, dd, J=2.3, 0.7 Hz), 8.49 (1H, dd, J=8.3, 2.4 Hz), 8.08
(1H, dd, J=8.2, 0.8 Hz), 7.77 (1H, d, J=6.2 Hz), 7.72 (1H, br),
7.37 (1H, d, J=9.5 Hz), 5.33 (1H, m), 2.58 (2H, m), 2.41 (3H, d,
J=2.0 Hz), 2.40 (2H, m), 1.82 (2H, m), 1.26 (3H, s).
Additional compounds representative of the present invention were
prepared according to the procedure of Example 18 by substituting
the appropriate starting materials, reagents and reaction
conditions and include compounds selected from (wherein MS
represents mass spec as MH.sup.+, unless otherwise indicated, m.p.
represents melting point in .degree. C., and N/A indicates that the
data was not obtained):
TABLE-US-00020 Cpd Name m.p. MS 1114
6-[3-cyano-1-cyclobutyl-5-fluoro-6-(1,1,1- 213-215 485.0
trideuterium)methyl-1H-indol-2-yl]-N-[(2S)-
1,1,1-trifluoro(2-deuterium)propan-2-yl]pyridine- 3-sulfonamide
Example 19
6-[3-cyano-1-(cyclopropylmethyl)-5-fluoro-6-(1,1,1-trideuterium)methyl-1H--
indol-2-yl]-N-[(2-deuterium)propan-2-yl]pyridine-3-sulfonamide (Cmp
1119)
##STR00276##
Step A: t-Butyl 6-bromo-5-fluoro-1H-indole-1-carboxylate (30 g, 96
mmol, synthesized in a manner analogous to Example 8A) was added to
THF (110 mL), and the mixture was cooled to 0.degree. C. To this
mixture was added i-propylmagnesium chloride-lithium chloride
complex (90 mL, 117 mmol) portionwise over 10 minutes, and the
mixture was stirred at 0.degree. C. for 3 hours.
Iodomethane-d.sub.3 (8 mL, 128.6 mmol) was added, followed by a
solution of copper (I) cyanide (1.7 g, 19.0 mmol), lithium chloride
(1.6 g, 37.7 mmol), and THF (80 mL). The mixture was stirred at
room temperature for 18 hours. Diethyl ether (100 mL) and H.sub.2O
(100 mL) were added and the mixture was filtered through Celite,
rinsing the filter cake with diethyl ether (200 mL). The filtrate
was extracted with diethyl ether (2.times.80 mL). The combined
organic extracts were washed with brine (100 mL), dried with
Na.sub.2SO.sub.4, and concentrated using a rotary evaporator and
used without further purification.
##STR00277##
Step B: The residue from above was added to aq. NaOH (50%, 15 mL)
and MeOH (190 mL). The mixture was stirred at reflux for 1 hour and
then concentrated using a rotary evaporator. The residue was added
to CH.sub.2Cl.sub.2 (200 mL), H.sub.2O (200 mL), and the aqueous
layer was extracted with CH.sub.2Cl.sub.2 (2.times.200 mL). The
combined organic layers were dried with Na.sub.2SO.sub.4 and
concentrated. The residue was purified using silica gel
chromatography (2.times.80 g SiO.sub.2, 0% to 10% EtOAc in
hexanes), providing 5-fluoro-6-(methyl-d.sub.3)-1H-indole (13.6 g,
93% from t-butyl 6-bromo-5-fluoro-1H-indole-1-carboxylate).
##STR00278##
Step C: The compound from above,
5-fluoro-6-(methyl-d.sub.3)-1H-indole (5 g, 32.9 mmol), was
converted into 5-fluoro-6-(methyl-d.sub.3)-1H-indole-3-carbonitrile
(5.6 g, 95%) in a manner analogous to Example 6B.
##STR00279##
Step D: The compound from above,
5-fluoro-6-(methyl-d.sub.3)-1H-indole-3-carbonitrile (850 mg, 4.8
mmol), was converted into
1-(cyclopropylmethyl)-5-fluoro-6-(methyl-d.sub.3)-1H-indole-3-carbonitril-
e (901 mg, 81%) in a manner analogous to Example 6C.
##STR00280##
Step E: The compound from above,
1-(cyclopropylmethyl)-5-fluoro-6-(methyl-d.sub.3)-1H-indole-3-carbonitril-
e (169 mg, 0.73 mmol), was converted into
3-cyano-1-(cyclopropylmethyl)-5-fluoro-6-(methyl-d.sub.3)-1H-indol-2-ylbo-
ronic acid in a manner analogous to Example 7D
##STR00281##
Step F: The compound from above, 3-cyano
1-(cyclopropylmethyl)-5-fluoro-6-(methyl-d.sub.3)-1H-indol-2-ylboronic
acid, and 6-chloro-N-(2-deutero-propan-2-yl)pyridine-3-sulfonamide
(103 mg, 0.44 mmol, synthesized in a manner analogous to procedure
Example 21) were converted into Compound 1119 (101 mg, 53%) in a
manner analogous to Example 7E. Melting point: 216-218.degree. C.;
MS m/z 431.3 M+H.sup.+; .sup.1H NMR (500 MHz, acetone-d.sub.6)
.delta. 9.21 (1H, dd, J=2.4, 0.6 Hz), 8.51 (1H, dd, J. 8.3, 2.4
Hz), 8.21 (1H, dd, J=8.4, 0.6 Hz), 7.76 (1H, d, J=6.2 Hz), 7.42
(1H, d, J. 9.6 Hz), 6.86 (1H, br), 4.59 (2H, d, J=7.1 Hz), 1.20
(1H, m), 1.13 (6H, s), 0.38 (2H, m), 0.19 (2H, m).
Additional compounds representative of the present invention were
prepared according to the procedure of Example 19 by substituting
the appropriate starting materials, reagents and reaction
conditions and include compounds selected from (wherein MS
represents mass spec as MH.sup.+, unless otherwise indicated, m.p.
represents melting point in .degree. C., and N/A indicates that the
data was not obtained):
TABLE-US-00021 Cpd Name m.p. MS 1112
6-(3-cyano-1-cyclobutyl-5-fluoro-6-methyl-1H- 220-222 427.9
indol-2-yl)-N-[(2-deuterium)propan-2-yl]pyridine- 3-sulfonamide
Example 20
(S)-6-(3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl)-N-(1,1,1-
-trifluoropropan-2-yl)pyridine-3-sulfonamide (Cpd 704)
##STR00282##
Step A: To a solution of 6-bromo-5-fluoro-1H-indole (1.25 g, 5.3
mmol) in CH.sub.2Cl.sub.2 (10 mL) were added di-tert-butyl
dicarbonate (1.5 g, 7.0 mmol) and DMAP (13 mg, 0.1 mmol). The
reaction mixture was kept stirring for 2 hr at room temperature,
then partitioned between CH.sub.2Cl.sub.2 and water. The organic
layer was washed with water, brine and dried over Na.sub.2SO.sub.4
and evaporated. The resulting white solid, tert-butyl
6-bromo-5-fluoro-1H-indole-1-carboxylate, was air dried and used in
the next step without further purification. .sup.1H NMR (500 MHz,
CDCl.sub.3): .delta. 8.33 (1H, br s), 7.53 (1H, d, J=3.0 Hz) 7.20
(1H, d, J=8.5 Hz), 6.43 (1H, dd, J=3.5, 0.5 Hz), 1.59 (9H, s).
##STR00283##
Step B: To a solution of tert-butyl
6-bromo-5-fluoro-1H-indole-1-carboxylate (1.57 g, 5.0 mmol) in
dioxane (10 mL) was added a solution of Et.sub.2Zn in heptane (3.5
mL, 1.0M, 3.5 mmol) at room temperature. The mixture was kept
stirring for 30 min at 90.degree. C. and then cooled down to
0.degree. C., into which saturated sodium bicarbonate was added
dropwise. The mixture was then treated with water and extracted
with CH.sub.2Cl.sub.2. The organic layer was dried over
Na.sub.2SO.sub.4 and evaporated. The resulting oil was passed
through a silica plug and eluted with 10% ethyl acetate in hexane.
The eluent was evaporated to give tert-butyl
6-ethyl-5-fluoro-1H-indole-1-carboxylate as an oil which was
solidified upon standing (1.25 g, 95%).
##STR00284##
Step C: Into a solution of tert-butyl
6-ethyl-5-fluoro-1H-indole-1-carboxylate (0.93 g, 3.5 mmol) and
tri-isopropyl borate (1.2 mL, 5.25 mmol) in THF (7 mL) at
-78.degree. C. was added LDA (1.5 M in cyclohexane, 2.8 mL, 4.2
mmol) under nitrogen. The mixture was stirred at -78.degree. C. for
15 min, then 2 hr at 0.degree. C. The reaction was quenched by
addition of acetic acid (0.24 mL, 4.2 mmol) over a period of 15
min, followed by removal of solvents by rotary evaporation. The
resulting boronic acid (>90% pure by LCMS) was used in the next
step without further purification.
##STR00285##
Step D: Into a solution of
1-(tert-butoxycarbonyl)-6-ethyl-5-fluoro-1H-indol-2-ylboronic acid,
prepared as above,
(S)-6-chloro-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide
(0.91 g, 3.15 mmol) and PdCl.sub.2dppf (0.23 g, 0.31 mmol) in
acetonitrile (21 mL) was added a solution of potassium carbonate
(2.0 M, 7 mL, 14 mmol). The mixture was stirred at 50.degree. C.
overnight, cooled to room temperature, and then quenched by
addition of HCl (1 N) in ice-water to pH .about.8. The mixture was
extracted with ethyl acetate. The combined organics were dried over
Na.sub.2SO.sub.4 and concentrated. The resulting crude mixture was
used in the next step without further purification.
##STR00286##
Step E: A mixture of (S)-tert-butyl
6-ethyl-5-fluoro-2-(5-(N-(1,1,1-trifluoropropan-2-yl)sulfamoyl)pyridin-2--
yl)-1H-indole-1-carboxylate, prepared as above, and pyrrolidine
(1.5 mL, 18 mmol) in acetonitrile (15 mL) was stirred at 50.degree.
C. for 2 hr. The solvents were then evaporated and the residue was
partitioned between ethyl acetate and HCl (1N). The aqueous phase
was further extracted with ethyl acetate. The combined organics
were washed with 1N HCl and brine. After concentration, the crude
mixture was triturated with CH.sub.2Cl.sub.2/hexane to provide
(S)-6-(6-ethyl-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyri-
dine-3-sulfonamide as light yellow solids (1.16 g, 80% yield from
(S)-6-chloro-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide).
##STR00287##
Step F: To a solution of
(S)-6-(6-ethyl-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyri-
dine-3-sulfonamide (0.22 g, 0.53 mmol) in a mixture of DMF (0.5 mL)
and acetonitrile (0.5 mL) was added chlorosulfonyl isocyanate
dropwise at -50.degree. C. The reaction mixture was kept stirring
at 0.degree. C. for 0.5 hr and then quenched with ice, following by
pouring into water. After 0.5 hr stirring at room temperature, the
resulting solid was collected by filtration and washed with water,
hexane and CH.sub.2Cl.sub.2. After air drying,
(S)-6-(3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluoro-
propan-2-yl)pyridine-3-sulfonamide was obtained and used in the
next step without further purification.
##STR00288##
Step G: A mixture of
(S)-6-(3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-
-yl)pyridine-3-sulfonamide (0.22 g, 0.5 mmol), prepared as above,
2-bromopyrimidine (0.167 g, 1.0 mmol), potassium carbonate (0.212
g, 1.5 mmol) and copper (I) iodide (20 mg, 0.1 mmol) were mixed
with DMF (2.5 mL). The system was evacuated and replaced with an
argon atmosphere. The reaction mixture was stirred at 110.degree.
C. for 70 hr, then cooled to 0.degree. C., diluted with ethyl
acetate and neutralized with 1N HCl. The ethyl acetate layer was
washed with water, brine, dried over Na.sub.2SO.sub.4, filtrated
through silica gel pad and evaporated. The crude product was
triturated with CH.sub.2Cl.sub.2 and hexane and was further
recrystallized from ethyl acetate and hexane. After air drying, the
off-white solid
(S)-6-(3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl)-N-(1,1,-
1-trifluoropropan-2-yl)pyridine-3-sulfonamide was obtained. Melting
point: 195-198.degree. C.; MS m/z 519.1 M-1-H.sup.+; .sup.1H NMR
(500 MHz, acetone-d.sub.6): .quadrature. 8.90 (1H, dd, J=2.5, 1.0
Hz), 8.83 (2H, d, J=4.5 Hz), 8.49 (1H, dd, J=8.0, 2.5 Hz), 8.16 (1
H, t, J=6.5 Hz), 8.15 (1 H, d, J=9.0 Hz), 7.68 (1 H, br s),
7.57-7.54 (2H, m), 4.32 (1 H, br s), 2.85 (2 H, q, J=7.5 Hz), 1.29
(3 H, t, J=7.5 Hz), 1.28 (3 H, d, J=7.2 Hz).
Additional compounds representative of the present invention may be
prepared according to the procedure of Example 20 by substituting
the appropriate starting materials, reagents and reaction
conditions and include compounds selected from (wherein MS
represents mass spec as MH.sup.+, unless otherwise indicated, m.p.
represents melting point in .degree. C., and N/A indicates that the
data was not obtained):
TABLE-US-00022 Cpd Name m.p. MS 708
6-[5-chloro-3-cyano-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N- 193-196
507.3- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 724
6-{3-cyano-5-fluoro-1-[5-(trifluoromethyl)pyridin-2-yl]-1H- 216-218
55- 8.2 indol-2-yl}-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 739
6-[3-cyano-5-fluoro-6-methyl-1-(3-methylpyridin-2-yl)-1H- 219-221
518.- 2 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 740
6-{3-cyano-5-fluoro-6-methyl-1-[5-(trifluoromethyl)pyridin- 253-255
57- 2.2 2-yl]-1H-indol-2-yl}-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 742
6-[3-cyano-5-fluoro-1-(5-fluoropyridin-2-yl)-6-methyl-1H- 239-241
512.- 8 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 743
6-[3-cyano-1-(5-cyanopyridin-2-yl)-5-fluoro-6-methyl-1H- 276-277
528.9- indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 744
6-[3-cyano-5-fluoro-6-methyl-1-(5-nitropyridin-2-yl)-1H- 260-263
548.9- indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 777
6-[3-cyano-6-ethyl-5-fluoro-1-(5-fluoropyridin-2-yl)-1H- 210-212
535.8- indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 778
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-
205-208 5- 17.8
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 785
6-[5-chloro-3-cyano-6-methyl-1-(pyrimidin-2-yl)-1H-indol- 210-212
521.- 2 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 803
6-[5-chloro-3-cyano-6-methyl-1-(pyridin-2-yl)-1H-indol-2- 210-212
519.- 4 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 804
6-[5-chloro-3-cyano-1-(5-fluoropyridin-2-yl)-6-methyl-1H- 210-212
537.- 9 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 814
6-[3-cyano-5-fluoro-1-(3-fluoropyridin-2-yl)-6-methyl-1H- 193-198
521.- 5 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 815
6-[3-cyano-5-fluoro-1-(6-fluoropyridin-2-yl)-6-methyl-1H- 210-212
522.- 3 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 816
6-[3-cyano-5-fluoro-1-(4-methoxypyridin-2-yl)-6-methyl- 210-213
518.2 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 817
6-[3-cyano-5-fluoro-6-methyl-1-(pyrazin-2-yl)-1H-indol-2- 220-223
505.- 4 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 818
6-[3-cyano-6-cyclopropyl-5-fluoro-1-(5-fluoropyridin-2-yl)- 240-242
54- 8.2 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 819
6-[3-cyano-6-cyclopropyl-5-fluoro-1-(pyridin-2-yl)-1H- 220-223
530.1 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 820
6-[3-cyano-6-cyclopropyl-5-fluoro-1-(pyrimidin-2-yl)-1H- 236-240
531.2- indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 823
N-tert-butyl-6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H- N/A 451.3
indol-2-yl]pyridine-3-sulfonamide 824
N-tert-butyl-6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2- N/A 465.3
yl)-1H-indol-2-yl]pyridine-3-sulfonamide 843
6-[3-cyano-5-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl]-N- 174-179
487.2- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 844
6-[3-cyano-1-(3-fluoropyridin-2-yl)-5-methyl-1H-indol-2- 216-220
504.2- yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 845
6-[3-cyano-5-methyl-1-(pyrazin-2-yl)-1H-indol-2-yl]-N- 236-241
487.4 [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 847
6-[3-cyano-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-4- 180-186
504.4 methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 848
6-[3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl]-4- 199-204
505.1- methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 851
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2- 231-236
533- .5 yl]-4-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 852
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-
178-183 5- 32.2
4-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide
853 6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2-yl)-1H-indol-
219-226 505.- 1
2-yl]-4-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 854
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)-1H-indol-2- 192-197
504.- 0 yl]-4-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 855
N-tert-butyl-6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-
208-210 4- 79.6 1H-indol-2-yl]pyridine-3-sulfonamide 859
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2- N/A
533.1 yl]-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-3-
sulfonamide 860
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2- 169-179
477- .1 yl]-N-(1-methylcyclopropyl)pyridine-3-sulfonamide 861
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2- 193-200
555- .1 yl]-N-(1-methylcyclopropyl)-N-(pyrimidin-2-yl)pyridine-3-
sulfonamide 864
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2- N/A
531.5 yl]-N-[1-(trifluoromethyl)cyclopropyl]pyridine-3- sulfonamide
865 6-[3-cyano-5-fluoro-6-methyl-1-(5-methylpyrazin-2-yl)- N/A
518.5 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 866
6-[3-cyano-5-fluoro-1-(4-methoxypyrimidin-2-yl)-6- N/A 534.5
methyl-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 867
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2- 192-198
533- .1 yl]-5-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 870
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-
195-198 5- 32.1
5-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide
873 6-[3-cyano-5-fluoro-6-methyl-1-(4-methylpyrimidin-2-yl)- N/A
518.5 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 878
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2- 197-200
519- .1 yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 879
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-
178-182 5- 18.1
N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 880
6-[3-cyano-6-ethyl-5-fluoro-1-(5-fluoropyridin-2-yl)-1H- 209-216
536.1- indol-2-yl]-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 881
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2- 258-262
533- .1 yl]-2-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 882
N-tert-butyl-6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)- 200-205
478- .2 1H-indol-2-yl]pyridine-3-sulfonamide 884
N-tert-butyl-6-(3-cyano-6-ethyl-5-fluoro-1-phenyl-1H- 175-180 477.2
indol-2-yl)pyridine-3-sulfonamide 885
6-[3-cyano-5-fluoro-6-methyl-1-(5-methylpyridin-2-yl)-1H- 250-254
517.- 5 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 886
6-[3-cyano-5-fluoro-6-methyl-1-(4-methylpyridin-2-yl)-1H- 200-204
517.- 5 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 887
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-
219-224 5- 31.0
2-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide
888 6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-2-yl)-1H-indol-
201-204 519.- 2
2-yl]-5-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 889
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-2-yl)-1H-indol-2- 197-202
518.- 2 yl]-5-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 890
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2- 231-236
533- .2 yl]-4-methyl-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 891
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-2-yl)-1H-indol-2-yl]-
178-183 5- 32.2
4-methyl-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide
892 6-[3-cyano-5-fluoro-6-methyl-1-(pyridazin-3-yl)-1H-indol-
245-250 504.- 5
2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide
893 6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-3-yl)-1H-indol-2-
217-221 503.- 5 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 894
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-5-yl)-1H-indol- 198-202
504.- 5 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 895
6-[6-bromo-3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol- 224-226
569.1- 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 896
6-[3-cyano-5-fluoro-6-methyl-1-(pyrimidin-4-yl)-1H-indol- 214-219
504.- 5 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 897
6-[3-cyano-1-(pyrazin-2-yl)-5-(trifluoromethyl)-1H-indol-2- 255-258
54- 1.2 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 898
6-[3-cyano-1-(pyrazin-2-yl)-5-(trifluoromethoxy)-1H-indol- 191-195
557- .2 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 899
N-tert-butyl-6-[3-cyano-6-ethyl-5-fluoro-1-(pyrazin-2-yl)- 196-201
479- .4 1H-indol-2-yl]pyridine-3-sulfonamide 900
N-tert-butyl-6-[3-cyano-6-ethyl-5-fluoro-1-(3-fluoropyridin-
200-203 4- 96.2 2-yl)-1H-indol-2-yl]pyridine-3-sulfonamide 901
6-[3-cyano-6-fluoro-5-methyl-1-(pyrimidin-2-yl)-1H-indol- 125-130
505.- 2 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 903
6-[5-fluoro-6-methyl-1-(1,3-thiazol-2-yl)-1H-indol-2-yl]-N- 224-230
48- 4.5 [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 907
6-[6-acetyl-3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol- 220-221
533.- 0 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 908
6-[3-cyano-6-ethenyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol- N/A
517.2 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 914
6-[1-(5-chloropyrimidin-2-yl)-3-cyano-5-fluoro-6-methyl- 213-218
538.9- 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 915
6-[3-cyano-5-fluoro-6-methyl-1-(6-methylpyrazin-2-yl)- 211-215
518.5 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 917
6-[3-cyano-6-fluoro-5-methyl-1-(pyridin-2-yl)-1H-indol-2- 175-180
504.- 3
yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide 919
6-[3-cyano-6-fluoro-5-methyl-1-(pyrazin-2-yl)-1H-indol-2- 233-238
505.- 2 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 920
6-[3-cyano-1-(4-fluorophenyl)-5-methyl-1H-indol-2-yl]-N- 195-200
503.2- [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 921
6-(3-cyano-5-methyl-1-phenyl-1H-indol-2-yl)-N-[(2S)- 160-165 485.2
1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 922
6-[3-cyano-1-(pyrimidin-2-yl)-5-(trifluoromethyl)-1H-indol- 180-183
54- 1.2 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 923
6-[3-cyano-5-fluoro-6-methyl-1-(6-methylpyridin-2-yl)-1H- 219-225
517.- 5 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 924
6-[3-cyano-5-fluoro-1-(5-fluoropyrimidin-2-yl)-6-methyl- 244-248
522.5- 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 925
6-[3-cyano-5-fluoro-6-methyl-1-(5-methylpyrimidin-2-yl)- 179-184
518.5- 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 926
6-[3-cyano-5-fluoro-1-(4-fluoropyridin-2-yl)-6-methyl-1H- 229-233
521.- 5 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 927
6-[3-cyano-5-fluoro-6-(2-methyl-1,3-dioxolan-2-yl)-1- N/A 577.2
(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide 929
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrazin-2-yl)-1H-indol-2- 225-229
519.0- yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 930
6-[3-cyano-6-ethyl-5-fluoro-1-(6-fluoropyridin-2-yl)-1H- 205-211
536.0- indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 931
6-[3-cyano-6-ethyl-5-fluoro-1-(5-methylpyridin-2-yl)-1H- N/A 532.3
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 932
6-[3-cyano-6-ethyl-5-fluoro-1-(4-methylpyridin-2-yl)-1H- 188-190
532.1- indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 933
6-[3-cyano-5-fluoro-6-methyl-1-(pyridin-4-yl)-1H-indol-2- 250-255
503.- 5 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 934
6-[3-cyano-5-fluoro-6-methyl-1-(1,3-thiazol-2-yl)-1H- 203-208 509.5
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 935
6-[3-cyano-6-ethyl-5-fluoro-1-(1,3-thiazol-2-yl)-1H-indol- 187-191
523- .5 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 938
6-[6-bromo-3-cyano-5-fluoro-1-(pyrimidin-2-yl)-1H-indol- 266-268
531.2- 2-yl]-N-tert-butylpyridine-3-sulfonamide 941
6-[3-cyano-1-(1,6-dihydropyrimidin-2-yl)-6-ethyl-5-fluoro- N/A
521.3 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 942
6-[1-(5-chloropyrimidin-2-yl)-3-cyano-6-ethyl-5-fluoro-1H- 222-229
553- .3 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 943
6-[3-cyano-6-ethyl-5-fluoro-1-(2-methylpyrimidin-4-yl)- 138-146
533.1 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 944
6-[5-fluoro-1-(2-fluoropyridin-4-yl)-6-methyl-1H-indol-2- 176-180
496.- 5 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 945
6-[3-cyano-5-fluoro-1-(5-fluoropyridin-3-yl)-6-methyl-1H- 199-204
521.- 5 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 946
6-[3-cyano-6-ethyl-5-fluoro-1-(5-fluoropyrimidin-2-yl)-1H- 210-225
537- .0 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 947
6-[3-chloro-6-cyclopropyl-5-fluoro-1-(pyrimidin-2-yl)-1H- 248-250
540.- 0 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 948
6-[3-cyano-1-(5-fluoropyrimidin-2-yl)-5-methyl-1H-indol- 202-207
505.2- 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 949
6-[3-cyano-6-fluoro-1-(5-fluoropyrimidin-2-yl)-5-methyl- 226-231
523.2- 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 950
6-[3-cyano-1-(pyrimidin-2-yl)-6-(trifluoromethyl)-1H-indol- 206-210
54- 1.2 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 951
6-[3-cyano-1-(pyrazin-2-yl)-6-(trifluoromethyl)-1H-indol-2- 208-213
54- 1.2 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 952
6-[3-cyano-1-(pyridin-2-yl)-6-(trifluoromethyl)-1H-indol-2- 173-176
54- 0.2 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 953
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2- 207-214
491- .2 yl]-N-(cyclobutylmethyl)pyridine-3-sulfonamide 954
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-3-yl)-1H-indol-2-yl]-
205-212 5- 18.2
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 955
6-[3-cyano-6-ethyl-5-fluoro-1-(4-methoxypyridin-2-yl)-1H- 227-233
548.- 1 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 956
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2- 177-179
520- .2 yl]-N-[(2S)-1,1,1-trifluoro(2-deuterium)propan-2-
yl]pyridine-3-sulfonamide 957
6-[5-fluoro-6-methyl-1-(1,3-thiazol-4-yl)-1H-indol-2-yl]-N- N/A
484.5 [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 958
6-[5-fluoro-6-methyl-1-(1,3,4-thiadiazol-2-yl)-1H-indol-2- N/A
485.5 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 959
6-[5-fluoro-6-methyl-1-(1,3-thiazol-5-yl)-1H-indol-2-yl]-N- N/A
484.5 [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 960
6-[3-cyano-5-fluoro-6-methyl-1-(1,3-thiazol-4-yl)-1H- 184-189 509.5
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 961
6-[3-cyano-5-fluoro-1-(5-fluoro-6-methylpyridin-2-yl)-6- 240-246
535.5- methyl-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 962
6-[1-(6-chloropyridin-2-yl)-3-cyano-5-fluoro-6-methyl-1H- 253-257
537.- 9 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 963
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-5-yl)-1H-indol-2- 250-257
519- .2 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 964
6-[3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-4-yl)-1H-indol-2- 202-206
519- .2 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 965
6-[1-(3-chloropyridin-2-yl)-3-cyano-6-ethyl-5-fluoro-1H- 200-208
552.2- indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 966
6-[1-(5-chloropyridin-2-yl)-3-cyano-6-ethyl-5-fluoro-1H- 252-259
552.2- indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 971
6-[1-(3-chloropyridin-2-yl)-3-cyano-5-fluoro-6-methyl-1H- 221-225
537.- 9 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 973
6-[3-cyano-5-fluoro-6-methyl-1-(1,3-thiazol-5-yl)-1H- 234-238 509.5
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 974
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridin-4-yl)-1H-indol-2-yl]-
209-215 5- 18.3
N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 975
6-[3-cyano-6-ethyl-5-fluoro-1-(pyridazin-3-yl)-1H-indol-2- 240-247
519- .1 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 976
6-[3-cyano-6-ethyl-5-fluoro-1-(5-methylpyrimidin-2-yl)- 201-206
533.2 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 977
6-[3-cyano-5-fluoro-6-methyl-1-(1,3,4-thiadiazol-2-yl)-1H- 232-240
510- .5 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 983
6-[1-(5-chloropyridin-3-yl)-3-cyano-6-ethyl-5-fluoro-1H- 107-109
552.3- indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 984
6-{3-cyano-5-fluoro-1-[5-(hydroxymethyl)-1,3-thiazol-2- 180-185
539.5 yl]-6-methyl-1H-indol-2-yl}-N-[(2S)-1,1,1-trifluoropropan-
2-yl]pyridine-3-sulfonamide 985 methyl
2-[3-cyano-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1- N/A 567.5
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indol-1-yl]-
1,3-thiazole-5-carboxylate 986 methyl
2-[3-cyano-5-fluoro-6-methyl-2-(5-{[(2S)-1,1,1- N/A 567.5
trifluoropropan-2-yl]sulfamoyl}pyridin-2-yl)-1H-indol-1-yl]-
1,3-thiazole-4-carboxylate 987
6-[5-fluoro-6-methyl-1-(thiophen-3-yl)-1H-indol-2-yl]-N- N/A 483.5
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 988
6-[5-fluoro-1-(furan-3-yl)-6-methyl-1H-indol-2-yl]-N-[(2S)- N/A
467.4 1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 989
6-[5-fluoro-6-methyl-1-(thiophen-2-yl)-1H-indol-2-yl]-N- N/A 483.5
[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 990
6-[3-cyano-5-fluoro-6-methyl-1-(thiophen-2-yl)-1H-indol- 233-240
508.5- 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 991
6-[3-cyano-5-fluoro-1-(furan-3-yl)-6-methyl-1H-indol-2-yl]- 215-219
49- 2.4 N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
992 6-[3-cyano-5-fluoro-6-methyl-1-(thiophen-3-yl)-1H-indol-
196-203 508.5- 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 993
6-[1-(4-chloropyridin-2-yl)-3-cyano-6-ethyl-5-fluoro-1H- 185-190
552.2- indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 1000
6-[3-cyano-5-fluoro-6-methyl-1-(3-methylthiophen-2-yl)- 197.0-203.8
5- 23.5 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 1001
6-[3-cyano-1-(4,6-difluoropyridin-2-yl)-5-fluoro-6-methyl-
190.2-196.- 8 540.5
1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 1002
6-[3-cyano-6-ethyl-5-fluoro-1-(4-fluorophenyl)-1H-indol-2- 236-243
53- 5.6 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 1003
6-[1-(4-chlorophenyl)-3-cyano-6-ethyl-5-fluoro-1H-indol- 279-289
551.- 3 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- 553.3
sulfonamide 1004
6-[3-cyano-6-ethyl-5-fluoro-1-(4-methylphenyl)-1H-indol- N/A 531.7
2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- sulfonamide
1005 6-[3-cyano-6-ethyl-5-fluoro-1-(4-methoxyphenyl)-1H- 261-266
547.2 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 1006
6-{3-cyano-6-ethyl-5-fluoro-1-[4-(trifluoromethyl)phenyl]- 276-282
58- 5.7 1H-indol-2-yl}-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 1007
6-[3-cyano-1-(4-cyanophenyl)-6-ethyl-5-fluoro-1H-indol- 288-293
542.2- 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 1008
6-[3-cyano-6-ethyl-5-fluoro-1-(3-fluorophenyl)-1H-indol-2- 210-214
53- 5.3 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 1009
6-[3-cyano-6-ethyl-5-fluoro-1-(3-methylphenyl)-1H-indol- 193-198
531.- 4 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 1010
6-[3-cyano-6-ethyl-5-fluoro-1-(3-methoxyphenyl)-1H- 229-233
547.2
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 1011
6-{3-cyano-6-ethyl-5-fluoro-1-[3-(trifluoromethyl)phenyl]- 240-245
58- 5.3 1H-indol-2-yl}-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 1012
6-[3-cyano-1-(3-cyanophenyl)-6-ethyl-5-fluoro-1H-indol- 244-248
542.3- 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 1013
6-[3-cyano-5-fluoro-1-(2-fluoropyridin-4-yl)-6-methyl-1H-
243.4-246.9- 522.5
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 1014
6-[3-cyano-5-fluoro-1-(3-fluoropyridin-4-yl)-6-methyl-1H-
204.2-210.5- 522.5
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 1015
6-[3-cyano-5-fluoro-1-(6-fluoropyridin-3-yl)-6-methyl-1H-
246.8-252.7- 522.5
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 1016
6-[3-cyano-5-fluoro-6-methyl-1-(1-methyl-1H-pyrazol-4- 233.7-239.3
50- 7.5 yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 1017
6-[3-cyano-5-fluoro-6-methyl-1-(5-methyl-1,3-thiazol-2- 223.1-228.1
5- 24.5 yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 1018
6-[1-(3-chlorophenyl)-3-cyano-6-ethyl-5-fluoro-1H-indol- 195-198
551.- 3 2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3- 553.3
sulfonamide 1030
6-[3-cyano-5-fluoro-6-methyl-1-(3-methyl-1H-pyrazol-4- 238.8-244.0
50- 7.5 yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 1031
6-[3-cyano-5-fluoro-6-methyl-1-(5-methylthiophen-2-yl)- 246.8-249.4
5- 23.5 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 1032
6-[1-(5-chlorothiophen-2-yl)-3-cyano-5-fluoro-6-methyl- 244.8-247.4
5- 44.0 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 1033
6-[3-cyano-1-(5-cyanothiophen-2-yl)-5-fluoro-6-methyl- 182.0-184.6
53- 4.5 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 1034
6-[3-cyano-5-fluoro-6-methyl-1-(5-sulfamoylthiophen-2- 131.6-137.7
58- 8.6 yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 1035
6-[1-(5-acetylthiophen-2-yl)-3-cyano-5-fluoro-6-methyl- 235.6-238.7
5- 51.6 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 1038
6-[3-cyano-5-fluoro-6-methyl-1-(4-methyl-1,3-thiazol-2- 206.3-211.7
5- 24.5 yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-
yl]pyridine-3-sulfonamide 1055
6-[1-(2-acetylthiophen-3-yl)-3-cyano-5-fluoro-6-methyl- 208.7-212.4
5- 51.6 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 1056
6-[3-cyano-5-fluoro-6-methyl-1-(4-methylthiophen-3-yl)- 223.2-227.1
5- 23.5 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 1057
6-[1-(2-chlorothiophen-3-yl)-3-cyano-5-fluoro-6-methyl- 226.7-231.8
5- 44.0 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 1058
6-[3-cyano-5-fluoro-6-methyl-1-(5-methylthiophen-3-yl)- 210.5-215.2
5- 23.5 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 1059
6-[5-fluoro-6-methyl-1-(1,3-oxazol-2-yl)-1H-indol-2-yl]-N- N/A
469.4 [(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide 1060
6-[1-(5-cyanofuran-2-yl)-5-fluoro-6-methyl-1H-indol-2-yl]- N/A
493.4 N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-sulfonamide
1061 6-[3-cyano-1-(3,4-difluorophenyl)-6-ethyl-5-fluoro-1H- 229-235
N/A indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 1062
6-[1-(3-chloro-4-fluorophenyl)-3-cyano-6-ethyl-5-fluoro- 228-232
N/A 1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 1072
6-[3-cyano-1-(3-cyanofuran-2-yl)-5-fluoro-6-methyl-1H- 238.0-243.6
51- 8.5 indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 1073
6-[3-cyano-5-fluoro-6-methyl-1-(1,3-oxazol-2-yl)-1H- N/A 494.4
indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 1074
6-[3-cyano-1-(4-cyano-1,3-oxazol-2-yl)-5-fluoro-6-methyl-
212.2-216.9- 519.4
1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-
3-sulfonamide 1075
6-[3-cyano-6-ethyl-5-fluoro-1-(2-fluorophenyl)-1H-indol-2- N/A
535.5 yl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-
sulfonamide 1078 6-{3-cyano-6-[(1,1-dideuterium)ethyl]-5-fluoro-1-
180-182 521.5 (pyrimidin-2-yl)-1H-indol-2-yl}-N-[(2S)-1,1,1-
trifluoropropan-2-yl]pyridine-3-sulfonamide 1079
6-{3-cyano-6-[(1,1-dideuterium)ethyl]-5-fluoro-1- 180-182 522.5
(pyrimidin-2-yl)-1H-indol-2-yl}-N-[(2S)-1,1,1-trifluoro(2-
deuterium)propan-2-yl]pyridine-3-sulfonamide 1098
6-[3-cyano-6-cyclopropyl-4-fluoro-1-(pyrimidin-2-yl)-1H- 198-200
545.- 3
indol-2-yl]-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine-
3-sulfonamide 1101
N-[5-(3-cyano-6-cyclopropyl-5-fluoro-1-phenyl-1H-indol- 249-250
489.3- 2-yl)pyridin-2-yl]-2-methylpropane-2-sulfonamide 1107
6-[3-cyano-5-fluoro-6-(1,1,1-trideuterium)methyl-1- 200-202 508.9
(pyrimidin-2-yl)-1H-indol-2-yl]-N-[(2S)-1,1,1-trifluoro(2-
deuterium)propan-2-yl]pyridine-3-sulfonamide 1108
N-tert-butyl-6-(3-cyano-5-fluoro-6-methyl-1-phenyl-1H- 200.6-202.4
46- 3.3 indol-2-yl)pyridine-3-sulfonamide 1117
N-tert-butyl-6-(3-cyano-6-cyclopropyl-5-fluoro-1-phenyl-
219.2-220.8 - 489.4 1H-indol-2-yl)pyridine-3-sulfonamide
BIOLOGICAL EXAMPLES
The following biological examples demonstrate the usefulness of the
compounds of the present invention for treating viral
infections.
Example 1
HCV Replicon Assay
The lack of reliable and readily accessible cell-culture and small
animal models permissive for HCV replication has limited the
development of new anti-HCV agents. Self-replicating subgenomic HCV
systems, termed HCV replicons, have been described and have been
widely used to assess the efficacy of anti-HCV inhibitors (see
Blight K J, et al., 2000, Efficient initiation of HCV RNA
replication in cell culture. Science 290:1972-1974; Blight K J, et
al., 2002, Highly permissive cell lines for subgenomic and genomic
hepatitis C virus RNA replication. J Virol 76:13001-13014; Ikeda M,
et al., 2002. Selectable subgenomic and genome-length dicistronic
RNAs derived from an infectious molecular clone of the HCV-N strain
of hepatitis C virus replicate efficiently in cultured Huh7 cells.
J Virol 76:2997-3006; Lohmann V, et al., 1999, Replication of
subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science
285:110-113; Pietschmann T, et al., 2002, Persistent and transient
replication of full-length hepatitis C virus genomes in cell
culture. J Virol 76:4008-4021; and, Pietschmann T. et al., 2001.
Characterization of cell lines carrying self-replicating hepatitis
C virus RNAs. J Virol 75:1 252-1264).
As described in U.S. Pat. No. 6,630,343, HCV inhibitors are
analyzed in the bicistronic replicon by quantitating replicon RNA
(GenBank Accession No. AJ242654) reduction and/or the Fluc reporter
signal. Replicon-containing cells may be cultured with a test
compound of the present invention for up to 3 days. Interferon
(IFN) .quadrature. is used as a positive control. In general, the
replicon IC.sub.50 values shown in Table 1 represent IC.sub.50
values determined by replicon RNA reduction.
As shown in Table 1, test compounds of the present invention may
demonstrate a replicon RNA reduction IC.sub.50 value of from
greater than about 2 .mu.M to about 5 .mu.M (*), an IC.sub.50 value
of between about 0.5 .mu.M to about 2 .mu.M (**), or an IC.sub.50
value of less than about 0.5 .mu.M (***).
TABLE-US-00023 TABLE 1 Replicon IC.sub.50 (.quadrature.M) Cpd
IC.sub.50 1 *** 2 *** 3 *** 4 * 5 *** 6 *** 7 ** 8 ** 9 *** 10 ***
11 ** 12 ** 13 *** 14 *** 15 ** 16 ** 17 ** 18 ** 19 * 20 ** 21 ***
22 ** 23 ** 24 *** 25 ** 26 ** 27 *** 28 * 29 *** 30 *** 31 *** 32
*** 33 *** 34 *** 35 *** 36 *** 37 *** 38 *** 39 * 40 ** 41 *** 42
*** 43 *** 44 *** 45 *** 46 *** 47 *** 48 *** 49 *** 50 *** 51 ***
52 *** 53 *** 54 *** 55 *** 56 *** 57 *** 58 *** 59 ** 60 *** 61
*** 62 *** 63 *** 64 *** 65 *** 66 *** 67 *** 68 *** 69 *** 70 ***
71 *** 72 *** 73 *** 74 *** 75 *** 77 ** 78 *** 79 *** 80 *** 81
*** 82 *** 83 *** 84 *** 85 *** 86 *** 87 *** 88 *** 89 *** 90 * 92
*** 93 *** 94 *** 95 *** 96 *** 97 ** 98 *** 99 *** 100 *** 101 ***
102 *** 103 *** 104 *** 105 *** 106 *** 107 *** 108 *** 109 *** 110
*** 111 *** 112 *** 113 *** 114 *** 115 *** 116 *** 117 ** 118 ***
119 *** 120 *** 121 *** 122 *** 123 *** 124 *** 125 *** 126 *** 127
*** 128 *** 129 *** 130 *** 131 *** 132 *** 133 *** 134 *** 135 ***
136 *** 137 *** 138 ** 139 ** 140 ** 141 ** 142 *** 143 *** 144 ***
145 *** 146 *** 147 *** 148 *** 149 *** 150 *** 151 *** 152 *** 153
*** 154 *** 155 *** 156 ** 157 *** 158 *** 159 *** 160 *** 161 ***
162 *** 163 ** 164 ** 165 ** 166 *** 167 *** 168 *** 169 *** 170
*** 171 *** 172 *** 173 *** 174 *** 175 *** 176 *** 177 *** 178 ***
179 *** 180 ** 181 *** 182 *** 183 ** 184 *** 185 *** 186 *** 187
*** 188 *** 189 *** 190 *** 191 ** 192 *** 193 *** 194 *** 195 ***
196 *** 197 *** 198 ** 199 *** 200 ** 201 *** 202 *** 203 *** 204
*** 205 *** 206 ** 207 ** 208 *** 209 *** 210 *** 211 *** 212 ***
213 *** 214 *** 215 ** 216 ** 217 * 218 *** 219 *** 220 *** 221 ***
222 *** 223 *** 224 *** 225 *** 226 *** 227 *** 228 *** 229 *** 230
*** 231 *** 232 *** 233 *** 234 *** 235 *** 236 *** 237 *** 238 ***
239 ** 240 *** 241 *** 242 ** 243 ** 244 * 245 *** 246 ** 247
**
248 *** 249 *** 250 *** 251 ** 252 *** 253 *** 254 ** 255 *** 256
*** 257 ** 258 *** 259 *** 260 *** 261 *** 262 *** 263 *** 264 **
265 ** 266 ** 267 *** 268 *** 269 ** 270 * 271 ** 272 ** 273 ***
274 * 275 * 276 * 277 *** 278 ** 279 ** 280 ** 281 ** 282 ** 283 *
284 ** 285 ** 286 ** 287 ** 288 ** 289 ** 290 * 291 ** 292 ** 293
** 294 ** 295 * 296 * 297 ** 298 ** 299 * 300 *** 301 *** 302 ***
303 *** 304 *** 305 *** 306 ** 307 *** 308 ** 309 *** 310 *** 311
*** 312 ** 313 *** 314 *** 315 *** 316 *** 317 *** 318 *** 319 **
320 ** 321 ** 322 * 323 *** 324 *** 325 *** 326 *** 327 *** 328 ***
329 *** 330 *** 331 *** 332 *** 333 *** 334 *** 335 *** 336 *** 337
** 338 *** 339 *** 340 *** 341 *** 342 ** 343 * 344 *** 345 *** 346
*** 347 ** 348 ** 349 ** 350 ** 351 *** 352 *** 353 *** 354 *** 355
*** 356 *** 357 *** 358 *** 359 *** 360 *** 361 *** 362 *** 363 ***
364 *** 365 *** 367 ** 368 *** 369 *** 370 *** 371 *** 372 *** 373
*** 374 *** 375 *** 376 *** 377 *** 378 *** 379 *** 380 *** 381 ***
382 *** 383 *** 384 *** 385 *** 386 *** 387 *** 388 ** 389 ** 390
** 391 *** 392 *** 393 *** 394 *** 395 *** 396 *** 397 *** 398 ***
399 *** 400 *** 401 *** 402 *** 403 ** 404 *** 405 *** 406 *** 407
*** 408 *** 409 *** 410 *** 411 ** 412 *** 413 *** 414 *** 415 ***
416 *** 417 ** 418 ** 419 ** 420 ** 421 *** 422 *** 423 *** 424 ***
425 ** 426 *** 427 *** 428 *** 429 *** 430 *** 431 *** 432 *** 433
*** 434 *** 435 *** 436 *** 437 *** 438 *** 439 *** 440 *** 441 ***
442 *** 443 *** 444 *** 445 *** 446 *** 447 *** 448 ** 449 *** 450
*** 451 *** 452 *** 453 *** 454 *** 455 *** 456 *** 457 *** 458 ***
459 *** 460 *** 461 *** 462 *** 463 *** 464 ** 465 *** 466 *** 467
*** 468 *** 469 ** 470 *** 471 *** 472 *** 473 *** 474 *** 475 ***
476 *** 477 *** 478 *** 479 *** 480 *** 481 *** 482 *** 483 *** 484
*** 485 *** 486 *** 487 *** 488 *** 489 ** 490 * 491 ** 492 *** 493
*** 494 * 495 * 496 ** 497 *** 498 ** 499 ***
500 *** 501 *** 502 *** 503 ** 504 *** 505 *** 506 *** 507 ** 508
*** 509 *** 510 ** 511 *** 512 *** 513 *** 514 *** 515 *** 516 ***
517 *** 518 *** 519 *** 520 ** 521 *** 522 *** 523 ** 524 *** 525
** 526 *** 527 *** 528 *** 529 *** 530 *** 531 *** 532 *** 533 ***
534 *** 535 *** 536 *** 537 *** 538 *** 539 *** 540 *** 541 *** 542
*** 543 *** 544 *** 545 *** 546 ** 547 *** 548 ** 549 *** 550 ***
551 *** 552 ** 553 *** 554 *** 555 *** 556 *** 557 *** 558 *** 559
*** 560 *** 561 ** 562 *** 563 ** 564 *** 565 *** 566 ** 567 ***
568 * 569 ** 570 ** 571 *** 572 *** 573 *** 574 *** 575 *** 576 ***
577 *** 578 *** 579 *** 580 *** 581 *** 582 *** 583 *** 584 ** 585
*** 586 *** 587 *** 588 *** 589 *** 590 *** 591 *** 592 *** 593 ***
594 *** 595 *** 596 *** 597 *** 598 *** 599 *** 600 *** 601 *** 602
** 603 *** 604 *** 605 *** 606 *** 607 *** 608 *** 609 *** 610 ***
611 *** 612 *** 613 *** 614 ** 615 *** 616 *** 617 *** 618 *** 619
*** 620 *** 621 *** 622 *** 623 ** 624 *** 625 *** 626 *** 627 ***
628 *** 629 * 630 *** 631 *** 632 *** 633 *** 634 *** 635 *** 636
*** 637 *** 638 *** 639 *** 640 *** 641 *** 642 *** 643 *** 644 ***
645 *** 646 * 647 ** 648 *** 649 *** 650 *** 651 *** 652 *** 653
*** 654 *** 655 *** 656 *** 657 *** 658 *** 659 *** 660 *** 661 ***
662 *** 663 ** 664 *** 665 ** 666 *** 667 *** 668 *** 669 *** 670
*** 671 *** 672 *** 673 *** 674 *** 675 *** 676 *** 677 *** 678 ***
679 *** 680 *** 681 *** 682 *** 683 *** 684 ** 685 ** 686 *** 687
*** 688 *** 689 ** 690 ** 691 *** 692 *** 693 *** 694 * 695 *** 696
*** 697 *** 698 *** 699 *** 700 *** 701 *** 702 *** 703 *** 704 ***
705 *** 706 *** 707 *** 708 *** 709 *** 710 *** 711 *** 712 * 713
*** 714 *** 715 *** 716 *** 717 ** 718 *** 719 ** 720 *** 721 **
722 *** 723 *** 724 ** 725 *** 726 *** 727 *** 728 * 729 *** 730
*** 731 *** 732 *** 733 *** 734 *** 735 *** 736 *** 737 *** 738 ***
739 *** 740 *** 741 ** 742 *** 743 *** 744 *** 745 *** 746 *** 747
*** 748 *** 749 *** 750 ***
751 *** 752 *** 753 *** 754 *** 755 *** 756 *** 757 ** 758 *** 760
*** 761 *** 762 *** 763 ** 764 *** 765 *** 766 *** 767 *** 768 ***
769 *** 770 *** 771 *** 772 *** 773 ** 774 *** 775 ** 776 *** 774
*** 775 ** 776 *** 777 *** 778 *** 780 *** 781 *** 782 *** 783 *
784 *** 785 *** 786 *** 787 *** 788 *** 789 *** 790 *** 791 * 793
*** 794 * 795 *** 796 *** 797 *** 798 ** 799 *** 800 *** 801 ***
802 *** 803 *** 804 *** 805 ** 806 *** 807 *** 808 *** 809 *** 810
*** 811 *** 812 * 813 ** 814 *** 815 *** 816 *** 817 *** 818 ***
819 *** 820 *** 821 *** 822 *** 823 ** 824 *** 825 *** 826 *** 827
*** 828 * 829 *** 830 *** 831 *** 832 *** 833 ** 834 * 835 *** 836
** 837 *** 838 *** 839 *** 840 *** 841 *** 842 *** 843 *** 844 ***
845 *** 846 *** 847 *** 848 *** 849 *** 850 *** 851 *** 852 *** 853
*** 854 *** 855 *** 856 *** 857 *** 858 ** 859 ** 860 *** 861 * 862
*** 863 *** 864 *** 865 *** 866 ** 867 *** 868 *** 869 ** 870 ***
871 *** 872 *** 873 *** 874 *** 875 *** 876 *** 877 *** 878 *** 879
*** 880 *** 881 *** 882 *** 883 *** 884 *** 885 *** 886 *** 887 ***
888 *** 889 *** 890 *** 891 *** 892 *** 893 *** 894 *** 895 *** 896
*** 897 *** 898 ** 899 *** 900 ** 901 *** 902 ** 903 *** 904 ***
905 *** 906 *** 907 *** 908 *** 909 ** 910 *** 911 *** 912 * 913
*** 914 *** 915 *** 916 *** 917 *** 918 * 919 *** 920 *** 921 ***
922 *** 923 *** 924 *** 925 *** 926 *** 927 *** 928 *** 929 *** 930
*** 931 *** 932 *** 933 *** 934 *** 935 *** 936 *** 937 *** 938 ***
939 * 940 ** 941 ** 942 *** 943 ** 944 ** 945 *** 946 *** 947 ***
948 *** 949 *** 950 *** 951 *** 952 *** 953 *** 954 *** 955 *** 956
*** 957 ** 958 ** 959 *** 960 *** 961 *** 962 *** 963 *** 964 ***
965 *** 966 *** 967 *** 968 ** 969 *** 970 *** 971 ** 972 * 973 ***
974 *** 975 *** 976 *** 977 *** 978 * 979 * 980 ** 981 *** 982 *
983 *** 984 *** 985 *** 986 *** 987 *** 988 *** 989 *** 990 *** 991
*** 992 *** 993 *** 994 *** 995 *** 996 *** 997 *** 998 ** 999 ***
1000 *** 1001 ***
1002 *** 1003 *** 1004 *** 1005 *** 1006 ** 1007 *** 1008 *** 1009
*** 1010 *** 1011 ** 1012 ** 1013 *** 1014 *** 1015 *** 1016 ***
1017 *** 1018 *** 1019 *** 1020 *** 1021 *** 1022 *** 1023 *** 1024
*** 1025 *** 1026 ** 1027 *** 1028 * 1029 * 1030 ** 1031 *** 1032
*** 1033 *** 1034 ** 1035 ** 1036 * 1037 *** 1038 *** 1039 ** 1040
*** 1041 *** 1042 ** 1043 *** 1044 *** 1045 *** 1046 * 1047 ** 1048
** 1055 ** 1056 *** 1057 *** 1058 *** 1059 *** 1060 * 1061 *** 1062
*** 1063 *** 1064 *** 1065 *** 1072 ** 1073 *** 1074 *** 1075 ***
1078 *** 1079 *** 1080 ** 1081 *** 1082 *** 1083 *** 1084 *** 1085
*** 1086 *** 1087 *** 1088 *** 1092 *** 1093 ** 1094 *** 1095 **
1096 *** 1097 *** 1098 ** 1099 ** 1100 *** 1101 ** 1102 *** 1103 **
1104 *** 1105 *** 1106 *** 1107 *** 1108 *** 1109 *** 1110 *** 1111
*** 1112 *** 1113 *** 1114 *** 1115 *** 1116 *** 1117 *** 1118 ***
1119 ***
Example 2
Compound Activity Evaluation Using an HCV-Poliovirus Chimera
In an HCV-poliovirus (HCV-PV) chimera, the PV 5' UTR is replaced by
the HCV 5' UTR and partial (the first 123 amino acids) core coding
sequences (nucleotides 18 to 710 of HCV 1 b) (see Zhao W D and
Wimmer E, Genetic analysis of a poliovirus/hepatitis C virus
chimera: new structure for domain II of the internal ribosomal
entry site of hepatitis C virus, J. Virol., 2001, 75:3719-3730;
and, Zhao W D, Wimmer E and Lahser F C, Poliovirus/Hepatitis C
virus (internal ribosomal entry site-core) chimeric viruses:
improved growth properties through modification of a proteolytic
cleavage site and requirement for core RNA sequences but not for
core-related polypeptides, Journal of Virology, 1999,
73:1546-1554). As a consequence, the expression of poliovirus
proteins is under regulation of the HCV IRES. Poliovirus is a
picornavirus in which protein translation initiation is mediated by
an IRES element located in the 5' UTR. At the 5' end of the HCV-PV
chimeric genome, there is the cloverleaf-like RNA structure of PV,
which provides a cis-acting replication signal ending with the
genome-linked protein VPg. The replication kinetics of the HCV-PV
chimera matches that of the parental poliovirus (Mahoney) and can
result in cytopathic effects (CPE) in cell culture. Heptazyme (see
S C Gordon, B R Bacon, I M Jacobson, M I Shiffman, N H Afdhal, J G
McHutchison, T J Kwoh, and F A Dorr, A Phase II, 12-week study of
ISIS 14803, an antisense inhibitor of HCV for the treatment of
chronic hepatitis C, AASLD Abst. 795, Hepatology, 2002, 36:362A.),
a ribozyme that targets the HCV IRES, has been shown to be active
against the chimeric virus in cell culture (see Macejak D G, K L
Jensen, S F Jamison, K Domenico, E C Roberts, N Chaudhary, I von
Carlowitz, L Bellon, M J Tong, A Conrad, P A Pavco and L M Blatt,
Inhibition of hepatitis C virus (HCV)-RNA-dependent translation and
replication of a chimeric HCV poliovirus using synthetic stabilized
ribozymes, Hepatology, 2000, 31:769-776; and, Macejak D G, K L
Jensen, P A Pavco, K M Phipps, B A Heinz, J M Colacino and LM
Blatt, Enhanced antiviral effect in cell culture of type 1
interferon and ribozymes targeting HCV RNA, J Viral Hepatitis,
2001, 8:400-405).
A compound is tested for activity against the chimeric virus, by
seeding into HeLa cells and incubating the cells at 37.degree. C.
under 5% CO.sub.2 for 24 hours. The cells are then infected with
HCV-PV at a multiplicity of infection (MOI) of about 0.1 for 30 min
and then treated with a test compound for one day. The activity of
a test compound is determined by a change in viral RNA
production.
As shown in Table 2, test compounds of the present invention
demonstrate HCV-PV IC.sub.50 values of greater than from about 2
.mu.M to about 5 .mu.M (*), an IC.sub.50 value of between about 0.5
.mu.M to about 2 .mu.M (**), or an IC.sub.50 value of less than
about 0.5 .mu.M (***).
TABLE-US-00024 TABLE 2 HCV PV IC.sub.50 (.mu.M) Cpd IC.sub.50 5 ***
7 *** 10 *** 24 *** 29 *** 30 *** 31 *** 32 *** 34 *** 35 *** 36
*** 37 *** 38 *** 41 *** 42 *** 43 *** 44 *** 45 *** 49 *** 50 ***
51 *** 52 *** 53 *** 54 *** 60 *** 61 *** 64 *** 65 *** 68 *** 71
*** 72 *** 74 *** 78 *** 80 *** 81 *** 82 *** 83 *** 84 *** 85 ***
89 *** 92 *** 93 *** 94 *** 95 *** 96 *** 104 *** 110 *** 112 ***
113 *** 122 *** 124 *** 126 *** 129 *** 132 *** 135 *** 145 *** 178
*** 191 *** 198 ***
Without regard to whether a document cited herein was specifically
and individually indicated as being incorporated by reference, all
documents referred to herein are incorporated by reference into the
present application for any and all purposes to the same extent as
if each individual reference was fully set forth herein.
Although certain embodiments have been described in detail above,
those having ordinary skill in the art will clearly understand that
many modifications are possible in the embodiments without
departing from the teachings thereof. All such modifications are
intended to be encompassed within the claims of the invention.
* * * * *
References